Myosin

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MYOSIN AND ASSOCIATED MUSCLE PROTEINS

M-line
Muscle contraction
Skeletal
Smooth
Myosin
Associated proteins
Disorders
Heavy chains
Light chains
Molecular regions
Other: Non-muscle
Structure
External link: Myosin Homepage
Neuromuscular junction
Presynaptic
Postsynaptic
Smooth muscle
Thick filaments
Myosin
Non-myosin proteins
Thin filaments
Actin
Regulatory proteins
Tropomyosin
Troponin
Structural components
Z-line
Costameres

Dystrophin & related proteins
Muscle fiber structure & contraction

Skeletal muscle sarcomere

Click on structure for more information

THICK FILAMENTS

Myosin

Myosins: General
- Molecular motors
- Interact with actin filaments: Utilize energy from ATP hydrolysis to generate mechanical force
- Force generation: Associated with movement of myosin heads to tilt toward each other³

Myosin composition

Hexamer: Two trimers
- Heavy chains: Homodimer
- Each heavy chain binds 2 light chains
  - Essential light chain (ELC)
  - Regulatory light chain (RLC)
- Molecular weight 520,000
Heavy chains; 2 types
- Molecular weight: 220,000 each
- C-terminal half: α helical
- N-Terminal: Globular head
- Skeletal muscle isozymes: Multiple types; Clustered on Chromosome 17p13.1
- Cardiac isozymes (some also present in skeletal muscles): Chromosome 14

MYOSIN HEAVY CHAIN (MHC) ISOZYMES
Fiber type	MHC type	Tissue
I; Slow	Cardiacβ (MYH7)	Skeletal muscle Cardiac muscle: Fetal
II; Fast	IIa (MYH2) IIb (MYH4) IIx (MYH1)	Skeletal muscle
II; Fast	Embryonic (MYH3)	Skeletal muscle Fetal, not adult
IIc	IIa > I (MYH1) Embryonic Neonatal (MYH8)	Skeletal muscle Immature fibers
Super fast	MYH13 (II eom)	Extraocular muscle
Tonic	Slow tonic	Extraocular, intrafusil, tensor tympani
Fetal	MYH4
Cardiac, adult	Cardiac α (MYH6)	Cardiac; Some jaw muscles
Smooth	Smooth muscle (MYH11)	Aorta, Intestine
Non-muscle	Type A (MYH9)	Fibroblast, Endothelial, Macrophage
	Type B (MYH10)	Postsynaptic density
	Myosin 6 Myosin 7A Myosin 14 Myosin 15	Ear
	Myosin 5A	Skin; Immune cells
Also see: Myosin disorders External link: Myosin classes

Myosin light chains: 4 types
- Molecular weight: 20,000 each
- Chemical classes: 2; Heads associated with 1 of each
  - DTNB light chain: Phosphorylatable
    - Regulatory in heart , CNS , but not skeletal muscle
  - Alkalai light chain: Non-phosphorylatable
    - Skeletal muscle: Slow , Fast , and Fetal
- Properties
  - Bind Ca⁺⁺: High affinity
  - Phosphorylated by myosin light chain kinase (MLCK)
    - Changes conformation of myosin heads
    - Increased population placed close to thin filaments
    - Potentiates actin-myosin interaction at low Ca⁺⁺ levels
    - Related enzymes:
  - Regulation of myosin's ATPase activity
  - Regulate myosin assembly into thick filaments

Myosin molecular regions
- Tail: α helical coiled-coil long thin rod
  - C-terminus half of heavy chain
  - Forms thick filament backbone
  - Self-association of distal 60% of rod (light meromyosin moiety)
  - Inter-myosin bonds are ionic
  - C-terminal residues: Non-helical; Affect myosin assembly into filament backbone
- Head (S1 region): Globular
  - Molecular weight: 130,000
  - Composition
    - N-terminus of heavy chain
    - 2 Light chains: 1 of each class; Near junction with tail
  - Form cross-bridges
    - Arranged in helical pattern around thick filament
    - Bind actin when muscle contracts
  - Contains ATPase activity: 2 alkylated cysteine residues
  - Myosin in skeletal muscle has 2 heads; Other myosins may have only 1
  - Hinge region at tail-head junction
Thick filament: Contains > 200 myosin molecules
Myosin chaperone: unc-45B
- Actions
  - Required for myosin thick filament assembly & stability in cardiac & skeletal muscle
  - May contribute to myosin degradation via ubiquitin/proteasome system
- Loss-of-function mutations
  - Paralysis & Cardiac dysfunction
  - Reduced muscle myosin accumulation
  - Defective thick filament assembly
Myosin: Other
- Also see: Unconventional myosins
- External link

Non-myosin components in thick filament

C-protein
- Structure: Single polypeptide chain; Molecular weight 140,000
- Located in middle 1/3 of each half of A-band
- Binds to myosin tail region
- Maintains thick filaments in bundles of 200 to 400 molecules
- Fast , slow , and cardiac types
- Mutations in hypertrophic cardiomyopathy (CMH4)
- Immunization with C-protein induces experimental immune myositis¹
X protein
H protein
Titin
- Largest protein known: Molecular weight 3,000,000
- Major domains
  - Immunoglobulin: ~300 copies; Located in both A band (160 copies) & I band
  - Fibronectin; ~300 copies; Not prominent in A band
  - Phosphorylation sites: Near N & C-terminus; Associated with regulation of myogenesis
  - Kinase domain: Located at edge of M-line; Phosphorylates telethonin
  - Elastic region of titin: Links thick filament to Z line
    - Early phase of lengthening involves titin straightening
    - Further lengthening involves unfolding of peptide in I band regions
    - Gives rise to extensible properties of muscle
  - Z-disc: Z repeat; Associated with telethonin
- Location in muscle: Spans sarcomere from M line to Z line
- Functions
  - Directs assembly of contractile elements
  - Provides elasticity: via Serial spring elements
  - ? Myofibrillar cell signalling
    - Kinase domain: Carboxy-terminal
    - Phosphorylation sites: Associated with regulation of myogenesis
    - Calpain 3 protease-binding motif
- Diseases
  - Dilated cardiomyopathy 1G
  - Tibial distal myopathy
  - LGMD 2J
  - Myopathy with early respiratory failure (Edstrom)
  - Congenital myopathy + Fatal dilated cardiomyopathy
  - Hypertrophic myopathy (CMH 9)
  - Mouse: Muscular Dystrophy with Myositis (mdm)
- Other subclass of titin-like molecules
  - Present in smooth muscle
  - Smaller: 800 kD
  - Twitchins, Projectins, Mini-titins

M line

Function: Stabilizes thick-filament lattice
Components: Contains 3 proteins
- Creatine kinase
- M protein (165 kD)
- Myomesin (190 kD) : Binds to myosin, titin & light meromyosin

Disorders of myosin⁵

Acute quadriplegic myopathies: Myosin loss from muscle fibers
MYH IIa
- IBM3: Inclusion body myopathy with Contractures & Ophthalmoplegia
MYH7
- Cardiomyopathy
  - Hypertrophic
  - Hypertrophic with Cores
  - Dilated (CMD 1S)
- Hyaline body (Myosin storage) myopathy
- Distal myopathy (MPD1; Laing)
Hypertrophic cardiomyopathies
- MYH6
- MYL2
- MYL3
- Myosin light chain kinase 2 (MYLK2)
- Cardiac myosin binding protein-C
MYH8
- Distal arthrogryposis with cardiac myxomas
  - Pseudocamptodactyly & Trismus
MYH3: Distal arthrogryposis
- Freeman-Sheldon (DA2A)
- Sheldon-Hall (DA2B)
Hearing loss
- MYH6
- MYH7A
- MYH9
- MYH15
Other
- Elejalde disease
  l Myosin 5A (MYO5A; MYH12) ; Chromosome 15q21-q22
- May-Hegglin anomaly : Macrothrombocytopenia
  l Myosin heavy chain A (MYH9) ; Chromosome 22q12�13

THIN FILAMENTS

Actin
Regulatory proteins
Structural components
Z-line

Actin

Most abundant protein in cytoplasm of mammalian cells
G-actin (Globular)
- Spherical monomer
- Present at low ionic strength
- 2 domains: Large & small
- Nucleotide (ATP or ADP) binding in cleft between domains
- Each actin can bind to 4 other actins
- G-actin molecule contains a high-affinity myosin head binding site
- 2 α types expressed in muscle: Skeletal ; Cardiac
F-actin
- Helical polymer
- Self associates
  - Head to tail polymerization of asymmetric monomers
  - At physiologic ionic strength
  - Hydrolysis of ATP to ADP speeds polymerization & imposes polarity
  - Steady-state flux of subunits through F-actin
    - Net assembly at plus ends: Nearest the peripheral membrane; ATP-actin monomers added
    - Net disassembly at minus ends: Cytoplasmic end; ADP-actin monomers released
- Some actin-binding proteins inhibit polymerization
  - Cytosolic
    - Profilin 1 , and 2 : Concentrated at regions of new actin filament assembly
    - Thymosin β-4
    - Gelsolin : Severs actin filaments in presence of submicromolar calcium; Solates cytoplasmic actin gels
  - Z-line: Capping proteins inhibit polymerization at the most active, barbed (plus) end
- Other actin filament associated proteins
  - Actin bundling proteins: Plastins
  - α-actinin
Actin filaments
- Contain ~360 actin molecules
- 2 strands of F-actin twisted to form a double helix
- Flexible along long axis
- G-actin binds myosin heads
- Actin capped & thin filament stabilized by β-actinin
Disorders
- Skeletal actin: Congenital myopathy with excess of thin filaments; Nemaline rod myopathy
- Cardiac actin: Dilated cardiomyopathy

Regulatory proteins of thin filament

Tropomyosin
- Genral function: Regulates, with troponin, Ca⁺⁺ dependent muscle contraction
- Structure
  - 2 stranded α-helical coiled-coil protein
  - α and β subunits
- Interactions
  - Each tropomyosin dimer interacts with 7 actin molecules
  - β-Tropomyosin: Coiled-coil protein; Binds head to tail along length of actin filament
  - In relaxed state probably interferes with actin-myosin interaction
- Disease mutations
  - α1 subunit: Hypertrophic cardiomyopathy (CMH3)
  - α-tropomyosin-3 : Nemaline rod myopathy
  - Tropomyosin 2 (β-Tropomyosin; TPM2)
Troponin: Complex of 3 subunits
- General function: Prevents actin-myosin interaction in resting muscle
- TN-I
  - Types
    - Skeletal muscle
      - Slow (TNNI1)
      - Fast (TNNI2) : Distal arthrogryposis, Type 2B
    - Cardiac (TNNI3)
      - Disorders: Hypertrophic (CMH7) & Restrictive cardiomyopathies
  - Function: Inhibits actin-myosin interaction
- TN-C
  - Skeletal muscle types: Slow & Fast
  - Function: Binds Ca⁺⁺: Low & high affinity sites
  - One of most highly conserved proteins known
  - External link: Vanderbilt
- TN-T
  - Types: 3 genes expressed in tissue-specific manner
    - Skeletal muscle slow (TNNT1) & Fast (TNNT3)
    - Cardiac troponin T2 (TNNT2)
  - Function: Tropomyosin binding subunit
  - Mutations
    - TNNT1: Rod myopathy, Amish type
    - TNNT2: Hypertrophic cardiomyopathies
      - Mechanisms of action: May vary with specific gene defect
        
        Reduced Calcium sensitivity of force production: Increased Energetic load on the heart
        Increased Unloaded shortening velocity: Increased Energetic load on the heart
        Dominant-negative effect: Blocks Ca⁺⁺ activation of thin filament
    - TNNT3: Distal arthrogryposis (DA2B)
- Other disease relations
  - TN-T & TN-I levels increased in blood after myocardial infarction
Profilins
- Distribution: Present in 1:1 complex with monomeric actin
- Actions
  - Binds to PIP2: Inhibits formation of IP3 & DG
  - Low concentration: Enhance actin polymerization
  - High concentration: Inhibit actin polymerization
- Profilin 1
  - Present in many cells
  - Effects on cell division & survival during embryogenesis
- Profilin 2
  - Distribution: Highest levels in brain, skeletal muscle & kidney
Cofilin-2
- Skeletal muscle specific isoform
- Localized to thin filaments
- Exerts effect on actin, in part, through interactions with tropomyosins
- Disorder: Nemaline rod myopathy
Smooth & non-muscle cells also have
- Caldesmon
  - Lies in long pitch grooves of actin helix
  - Parallel and associated with tropomyosin
- Calponin

Thin filaments: Structural components & Associated structures

Nebulin
- Properties
  - Large protein: 600,000 to 800,000 kD
  - Abundant: 3% to 4% of myofibrillar protein
  - Contains 185 copies of a 35- to 40-amino acid module
- Location
  - Extends whole length of thin filament
  - 2 nebulin molecules per thin filament
- Function: Probably acts as inextensible template for thin filament assembly
- Diseases
  - Rod myopathy
  - Distal nebulin myopathy
Other
- Nebulin-related anchoring protein
  - Location
    - Skeletal muscle: Myotendinous junction
    - Cardiac muscle: Intercalated disc
  - Function: ? Anchors terminal actin filaments to subsarcolemmal protein complexes
- Nuclear Factor of Activated T Cells (NFATc): Translocates to nucleus with electrical stimulation
Z line components & structure
- Size
  - Thin in fast muscle
  - Thick in slow muscle
- α-Actinin
  - Structure
    - Homodimer: 97 kD subunits; Arranged in anti-parallel direction
    - Similar to spectrin
  - Muscle specific: Types 2 & 3
    - Type 2 present in all muscle fibers
    - Type 3 present in subset of type II fibers
    - Located only in: Z line; Costameres
    - Ca⁺⁺ insensitve
    - Type 3 interacts with: Calsarcin; Calcineurin
    - Form strong complex with F-actin: Anchor actin filaments
    - Also present in
      - Smooth muscle: Component of dense bodies & Plaques
      - Cardiac muscle
  - α-actinin disorders
    - α-actinin is Major component in rods
    - α-actinin-3 nonsense mutations
      - Heterozygotes: Very common in normal populations
      - Homozygotes: Arg577Ter mutation
        
        Variable frequency in different populations
        
        Europeans: 18%
        
        Asians: 25%
        
        African Bantu: < 1%
        
        Elite sprint athletes: Lower frequency of Ter mutation than controls; Absent in Females
        Endurance athletes: Higher frequency of Ter mutation
        
        No clinical disease phenotype
        
        No effect on muscular dystrophies
        
        ? Reduced power generation in normals
        Serum CK: Lower
      - Higher frequency of 577R allele than controls
        
        Male & female elite sprint athletes
        
        Male power athletes
    - α-actinin-4 : Focal segmental glomerulosclerosis
  - α-actinin in non-muscle cells
    - Epecially actin 1 & 4
    - Cytoskeletal isoform
    - Ca⁺⁺ sensitve
    - Location: Along microfilament bundles & adherens-type junctions
    - Function: Binds actin to the membrane
- Desmin
  - Circles periphery of Z line
  - Functions
    - May link Z lines of adjacent myofibrils
    - Integrates the contractile apparatus with sarcolemma & nucleus
  - Muscle-specific member of the intermediate filament family
  - Early myogenic marker in skeletal muscle & heart
    - Precedes MyoD family of myogenic helix-loop-helix regulators except myf5
  - Disorders
    - Myofibrillar myopathies: Normal desmin in aggregates in muscle fibers
    - Desmin mutations: Myofibrillar myopathies
- Desmuslin
  - Type VI intermediate filament protein
  - Colocalized with desmin
  - Interacts with α-dystrobrevin
  - Linkage between extracellular matrix & Z-discs: Structural support for muscle cell
  - Expressed in heart & Skeletal muscle
- Capping proteins: α1 ; α2 ; β subunits
  - Caps the barbed end of actin filaments
  - Regulates the growth of the actin filament at the barbed end
- Calpain 3: LGMD 2A
- Calcineurin: Binds to calsarcins
- Calsarcin 1 (Myozenin 2) : Adult cardiac & slow-twitch skeletal muscle
- Calsarcin 2 (Myozenin 1)
  - Fast skeletal muscle
  - Binds to filamin C
- CapZ : β1 isoform
- Myopalladin (161650)
  - Tethers nebulin in skeletal muscle to α-actinin at Z lines
  - Also present in I-band of cardiac muscle & nucleus
- Myotilin : Interacts with α-actinin
- Nebulin: C-terminal region
- Supervilin : Actin binding protein; ? Link with membrane
- Telethonin : LGMD 2G
Costameres⁴
- Location
  - Subsarcolemmal
  - Circumferentially align in register with the Z disk
- Functions
  - Transduce forces generated by myofibrils
    - Across sarcolemma
    - To extracellular matrix & other muscle cells
  - Coordinate organized folding of the sarcolemma
    - Minimizes stress on sarcolemmal during muscle contraction or stretch
  - Homology: Focal adhesions expressed by non-muscle cells
- Components
  - Aciculin
  - γ-Actin
  - α-Actinin
  - Ankyrins
  - CapZ : β2 isoform
  - Collagens: Types IV & XIII
  - Chisel (Csl/Smpx) : Upregulated in response to passive stretch
  - Desmin: Physical link between Z-disk & sarcolemma
  - Dystroglycan
  - Dystrophin
    - Coupling between sarcolemma and γ-actin filaments of costameres
    - Loss of dystrophin leads to disorganized costameric lattice
  - Integrins: α7 & β1
  - Laminin-2
  - Melusin : Prevents cardiac dilation during chronic pressure overload by sensing mechanical stress
  - Muscle-specific LIM Protein (MLP): Dilated cardiomyopathy 1M
  - Neuronal Nitric Oxide Synthase (nNOS)
  - Raver1
    - Localized to costamere in adult skeletal muscle
    - Redistributes from nucleus to cytosol during myotube formation/differentiation
  - Spectrin
  - Syncoilin
  - Synemin
  - Syntrophin
  - Talins : Links vinculin to integrins
  - E-Tropomodulin (E-Tmod)
  - Type-II SH2-domain containing inositol 5-phosphatase (SHIP2)
  - Vimentin
  - Vinculin
    - Focal adhesion protein
    - Vinculin splice variant (metavinculin) mutations cause dilated cardiomyopathy

SKELETAL MUSCLE CONTRACTION & RELAXATION

Resting muscle

Myosin binding sites on actin are obscured
- 1 Tropomyosin covers the myosin binding sites of 7 G-actin residues
- Tropomyosin resides in grooves of F-actin helix
Myosin in high-energy conformational state
High energy state produced by ATP

Muscle contraction

Sarcolemma depolarization: Spreads to internal T tubule system
Cytosolic Ca⁺⁺ Increased
- Voltage-gated Ca⁺⁺ channels in SR membranes opened
- Movement of cisternal Ca⁺⁺ into the sarcoplasm
- Contraction when Ca⁺⁺ concentration > 1 to 5 μM
Myosin binding sites on actin become available
- Troponin subunit C binds Ca⁺⁺
- Troponin undergoes conformational change
- Attached tropomyosin moved
  - More deeply into helix groove of F-actin
  - Away from myosin binding sites on actin
  - Uncovers myosin binding sites on G-actin subunits
  - G-actin subunits available to interact with myosin headpieces
Actin-myosin complex formed
Binding influenced by phosphorylation of myosin light chain
Dissociation of Pi and ADP
Conversion of myosin to low-energy conformational state
Rapid myosin conformational changes about its hinge points
Translocation of attached thin filament toward the M line of sarcomere

Muscle relaxation

Sarcoplasmic membrane & T tubule return to resting potential
- ~ 60 mV more positive outside
Sarcoplasmic Ca⁺⁺ reduced
- Pumped into the SR cisternae by ATP-driven Ca⁺⁺ pump
- For each ATP hydrolyzed, 2 Ca⁺⁺ ions moved out of the sarcoplasm
- Calsequestrin , on cisternal surface of the SR membrane, binds Ca⁺⁺
- Binding decreases Ca⁺⁺ concentration in cisternae: Favors more Ca⁺⁺ accumulation
- Sarcoplasmic Ca⁺⁺ reduced to < 0.1 μM
  - 50-fold < KD for calcium binding to troponin-C
Sarcoplasmic Ca⁺⁺ also sequestered in mitochondrial matrix
- Via mitochondrial Ca⁺⁺ pump
- Driven by electron transport-generated chemiosmotic potential
- Aerobic conditions:
  - Pump uses electron transport energy to sequester calcium
  - Occurs in preference to ATP synthesis
Original conformational states of troponin and tropomyosin recur
Interaction between actin & myosin prevented

Muscle Fiber Contractile Types

	Type 1	Type 2
Color	Red	White
Twitch speed	Slow	Fast
Action	Tonic	Phasic
Oxidative enzymes	High Aerobic	Low Anaerobic
Mitochondria	Many	Few
Lipid content	Moderate	Low
Glycogen content	Low	Moderate
ATPase staining pH 9.4	Light	Dark
ATPase staining pH 4.3	Dark	Light

SMOOTH MUSCLE

Structure & Function

No organized sarcomere structure
Thin & thick filaments present in random, disorganized fashion
Sarcoplasmic reticulum: Poorly developed and sparse
Cytoplasmic Ca⁺⁺: Source is extracellular fluid
Caldesmon substitutes for troponin subunits
- Binds to tropomyosin & actin
- Inhibits myosin heads from moving
- Inhibition ê by:ê
  - Protein kinase C (PK-C): Phosphorylates caldesmon, or
  - Ca⁺⁺-Calmodulin complex: Binds to caldesmon & releases it from actin
- ê inhibition produces contraction
  - Tropomyosin changes location in helical grooves of F-actin
  - Actomyosin ATPase activity is stimulated.
- Calponin: Also inhibits myosin movement
  - Binds to actin
  - Calponin phosphorylation reduces actin binding
    - By Calmodulin-dependent kinase II or PK-C: Activated by Increased Ca⁺⁺
    - Calponin dephosphorylation: Rebinding to actin; Reduced myosin movement
Myosin regulation
- Smooth muscle myosin contains a regulatory light chain
- Myosin light chain kinase (MLCK)
  - Contains large & small (calmodulin) subunit
  - Activated by association of 4 Ca⁺⁺ ions with calmodulin subunit
  - Activated MLCK
    - Phosphorylates myosin regulatory chain
    - Stimulates ATPase activity
  - MLCK downregulated by
    - Phosphorylation of large subunit
    - Rise in cAMP & activation of a cAMP dependent protein kinase
- Hormonal activation of PK-C
  - Phosphorylates myosin light chains: At different site than MLCK
  - Inhibits ATPase activity
- Regulation of myosin activity in smooth muscle is slow

OTHER (UNCONVENTIONAL) MYOSINS

Myosins: General properties

Actin-based motor molecules with ATPase activity

Elejalde disease

l Myosin 5A (MYO5A; MYH12)

; Chromosome 15q21-q22

"Neuroectodermal melanolysosomal disease"
Silvery hair
Pigment abnormalities
CNS: Seizures; Severe hypotonia; Mental retardation
Mouse model: 'Dilute lethal'
Also see: Griscelli syndrome

Hearing loss with abnormal unconventional myosin heavy chains

Myosin 6 ; Chromosome ?
- In inner ear hair cells
- Mouse model: Snell's walzer
Myosin 7A
- Deafness, non-syndromic (DFNB2)
- Usher syndrome : Congenital deafness; Vestibular areflexia; Progressive retinitis pigmentosa.
Myosin heavy chain A (MYH9) : Fechtner syndrome
- Hematologic: Thrombocytopenia; Large platelets; Leukocyte inclusions ('D�hle-like' bodies)
- Sensorineural deafness: Alport-like
- DFNA 17
Myosin 14
- Deafness, Autosomal dominant (DFNA4)
Myosin 15
- Ceafness: Congenital Recessive (DFNB3)
- Mouse model: Shaker-2

May-Hegglin anomaly

Myosin heavy chain A (MYH9) ; Chromosome 22q12�13
- Macrothrombocytopenia

Other myosins

Myosin 1A : Cell migration, neurite outgrowth & vesicular transport
Myosin 1B : Movement of organelles along actin filaments
Myosin 1C
Myosin 1D
Myosin 1E
Myosin 1F
Myosin 5B
Myosin 7B
Myosin 9B : Leukocytes & other tissues
Myosin 10 : Associates with regions of dynamic actin

Griscelli syndrome²

l RAB27A

; Chromosome 15q21

RAB27A protein
- Effector of cytotoxic granule exocytosis
- Interacts with MYO 5A
Clinical
- Pigmentary dilution
  - Skin: Diffuse pigmentation
  - Hair: Silvery; Clumps of pigment in shafts
  - Melanocytes: Accumulation of melanosomes
- Immunologic
  - Absent delayed-type cutaneous hypersensitivity
  - Acute phases of uncontrolled lymphocyte and macrophage activation
  - Impaired natural-killer cell function
  - Hemophagocytic syndrome
- Neurological
  - Onset after immune disorders
  - Due to lymphocytic and histiocytic infiltration of the brain
- Prognosis: Death unless bone marrow transplantation
Mouse model: ashen
Also see: Elejalde syndrome

Return to Myopathies
Return to Neuromuscular home page

References
1. J Neuroimmunol 1999;98:130-135
2. Am J Hum Genet 2002;August
3. PNAS 2002;99:14801�14806
4. J Biol Chem 2003;Online Jan 29
5. Neuromuscul Disord 2007; Apr 12

6/10/2008