Neuromuscular

Home, Search, Index, Links, Pathology, Molecules, Syndromes,
Muscle, NMJ, Nerve, Spinal, Ataxia, Antibody & Biopsy, Patient Info

MYOSIN & ASSOCIATED MUSCLE PROTEINS

M-line
Muscle contraction
  Skeletal
  Smooth
Myosin
  Associated proteins
  Disorders
  Fiber types
  Heavy chains
  Light chains
  Molecular regions
  Other: Non-muscle
  Structure
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

M Line Thick Filament Thick Filament Thick Filament Thick Filament Thin Filament Thin Filament Thin Filament Thin Filament Thin Filament Thin Filament Z-Line Z-Line Z-Line Muscle Fiber Structure
Click on structure for more information

A-band: Entire length of thick filaments
H-zone: Zone of thick filaments not associated with thin filaments
I-band: Zone of thin filaments not associated with thick filaments
M-line: Elements at center of thick filaments cross-linking them
Z-Disc: Disc between I-bands


THICK FILAMENTS

A-band: Entire length of thick filaments
H-zone: Zone of thick filaments not associated with thin filaments
M-line: Elements at the center of thick filaments cross-linking them



Myosin

Fiber types: ATPase stain vs Myosin Heavy Chain (MYH) Types

Images
Myosin HC types

Control Muscle


MYH stains = Green; Collagen IV = Red
Myosin Heavy Chain Types: Human Muscle Muscle Features: Other
Fiber
  Type
Myosin: Heavy
    Chain Types
Tissue Disorders Myonuclear
Domain Size
Cytochrome
Oxidase
NADH PAS &
Phosphorylase
Lipid ATPase
pH 4.3
ATPase
pH 4.6
ATPase
pH 9.4
I; Slow I (MYH7)
    (Cardiac β)
Skeletal muscle
  MYH7: 6 wks to Adult
Cardiac muscle
  Fetal
  Cardiomyopathy
MYH7
  Myopathies
Moderate High High Low High High High Moderate
IIa; Fast IIA (MYH2)
  ± I (MYH7)
Skeletal muscle
  MYH2: 24 wks to Adult
MYH2
  Myopathies
Larger Moderate Moderate High Moderate Absent
  or Low
Absent
  or Low
High
IIb; Fast IIA (MYH2)
  + IIX (MYH1)
  ± I (MYH7)
Skeletal muscle MYH1
  MYHM (Horse)
Largest Low Low Moderate Low Absent
  or Low
Moderate High
IIc I (MYH7)        
> IIA (MYH2)
Skeletal muscle
  Immature fibers
  Smaller Low High Moderate High Moderate Moderate Moderate-
  High
Fetal IIB (MYH4) Skeletal muscle
  Regeneration, Early
  Adult: Not normal
    Some LGMD
  Other adult mammals:
    2B fibers
  Small
Cardiac,
  adult
Cardiac α
    (MYH6)
Cardiac atria
  Jaw muscle, Some
MYH6
  Cardiomyopathies
Moderate Moderate Moderate
Central
  core
I (MYH7)        
+ IIX (MYH1)
Skeletal muscle
  Most fibers
  Moderate Moderate Moderate
Other Embryonic
    (MYH3) 9
Skeletal muscle
  Fetal, 6 to 24 wks
  Adult: Regeneration
    EOM; Spindle (Chain)
MYH3
  Arthrogryposis
Other Neonatal
    (MYH8)
9
Skeletal muscle
  Fetal, 7 wks to Birth
  Adult: Regeneration
    EOM; Spindle (Chain)
MYH8
  Arthrogryposis
Super
  fast
MYH13
  (II eom)
Extraocular muscle  
Tonic Slow tonic Extraocular, intrafusil,
  Tensor tympani
 
Smooth Smooth muscle
    (MYH11)
Aorta, Intestine MYH11
  Aneurysm (AAT4)
  Visceral myopathy 2
  MMIHS2
Other Myosin 6
  (MYO6)
Muscle
Inner ear
Hearing loss
Myosin 18B
  (MYO18B)
Muscle
  Cardiac & Skeletal
Skeletal +
  Myopathy
Myosin 19
  (MYO19)
Mitochondrial  
Non-
  muscle
Type A
    (MYH9)
Fibroblast
Endothelial cell
Macrophage
MYH9
  Hearing loss
  Thrombocytopenia
Type B
    (MYH10)
Postsynaptic density
Heart
 
Myosin 7A
Myosin 14
Myosin 15
Ear Hearing loss
Myosin 5A
Skin
Immune cells
 
MYO9B
PNS & CNS AR-CMT
Also see
  Fiber type disorders
  Myosin disorders
Non-myosin components in thick filament
  • C-proteins (MYBPC) 12
  • H protein (MYBPH)
    • Increased in muscle in ALS
  • 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
    • Isoforms
      • Several: Change during development
      • Most very large size
      • Largest isoform: Soleus
      • Smaller isoform: Psoas
      • 1 small isoform: Novex-3 (Xtn3)
        • Developmentally expressed in heart & skeletal muscle
        • Titin I-band region
    • Binding
    • Functions
      • Directs assembly of contractile elements
      • Provides sarcomere elasticity
        • via Serial spring elements
        • Prevents over-stretch of sarcomere
      • ? Myofibrillar cell signalling
        • Kinase domain: Carboxy-terminal
        • Phosphorylation sites: Associated with regulation of myogenesis
        • Calpain 3 protease-binding motif
    • Disease associations
    • Other subclass of titin-like molecules
      • Present in smooth muscle
      • Smaller: 800 kD
      • Twitchins, Projectins, Mini-titins
  • X protein
MyBPC1 labeled with GFP:
Localizes to C zones in A-band


From: C Weihl MD
M line Myosin: Disorders 5


THIN FILAMENTS

Actin
Regulatory proteins
  Tropomyosin
  Troponin
  Profilins
  Other
Structural components
Z-line
Costameres

I-band: Zone of thin filaments not associated with thick filaments

Actin Regulatory proteins of thin filament Thin filaments: Structural components & Associated structures

SKELETAL MUSCLE CONTRACTION & RELAXATION

Resting muscle Muscle contraction
  1. Sarcolemma depolarization: Spreads to internal T tubule system
  2. Cytosolic Ca++ Increased
  3. Myosin binding sites on actin become available
  4. Actin-myosin complex formed
  5. Binding influenced by phosphorylation of myosin light chain
  6. Dissociation of Pi and ADP
  7. Conversion of myosin to low-energy conformational state
  8. Rapid myosin conformational changes about its hinge points
  9. Translocation of attached thin filament toward the M line of sarcomere
Muscle relaxation
  1. Sarcoplasmic membrane & T tubule return to resting potential
  2. Sarcoplasmic Ca++ reduced
  3. Sarcoplasmic Ca++ also sequestered in mitochondrial matrix
  4. Original conformational states of troponin and tropomyosin recur
  5. Interaction between actin & myosin prevented
Muscle Fiber Contractile Types

SMOOTH MUSCLE

Structure & Function

OTHER (UNCONVENTIONAL) MYOSINS

Myosins: General properties Hearing loss with abnormal unconventional myosin heavy chains Other myosins & syndromes
Griscelli syndrome 2 (GS2) 2
  RAS-associated protein RAB27A (RAB27A) ; Chromosome 15q21.3
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. Acta Neuropathol 2012; Online July
7. Nat Commun 2016;7:11303
8. Gene 2016;576:385-394
9. Skelet Muscle 2015;5:22
10. Int J Mol Sci 2021;22:3058
11. Proc Natl Acad Sci U S A 2022;119:e2200215119
12. Front Genet 2022;13:896117
13. HGG Adv 2023;4:100213

7/18/2023