Biomedical Engineering Reference
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integrin
dystroglycan
dystrophin
costamere
melusin
spectrin
FAK
SR
calpain
calsarcin
filamin
Vinc
obscurin
desmin
PLD2
myotilin
FHL
PKN
zyxin
ankyrin
actin
GRK
MLP
titin
actinin
nebulette
actin
ERK
MuRF
enigma
myopalladin
cypher
PKC
cypher
calsarcin
PDE5A
titin
T−Cap
Rac1
PAK1
MLP
calcineurin
Cdc42
CapZ
PP2A
TN−I
myopodin
NFAT
Nucleus
Fig. 5.9
Z-disc proteins and partners, and their interactions (Source: [
373
]). Z disc is a lattice
of interdigitating proteins, such as nebulette, myopalladin, myotilin, filamin, CapZ, cypher,
myozenin-1,
-actinin, titin-cap (T-cap or
telethonin), muscle LIM protein (MLP, CLP, or CSRP3) that binds to actin and titin. Titin extends
over half a sarcomere. Titin crosses the Z disc. Titin then associates the Z disc to the M line,
both serving as sarcomere scaffolds (supporting and organizing actin and myosin filaments in
parallel arrays by crosslinking antiparallel actin and titin). Desmin filaments surround the Z disc,
connecting it to cortical (subsarcolemmal) costameres. The sarcomere is also linked to costameres
via sarcomeric
etc.
This proteic
complex
particularly
contains
α
α
-actinin and non-sarcomeric actin (i.e.,
γ
-actin).
strain sensor using its C-terminal protein Ser/Thr kinase domain at M line
38
to adapt
myocyte to changes in strain.
The titin kinase domain bears self-inhibition of its C-terminal regulatory tail that
blocks the ATP-binding site as well as auto-inhibition of the catalytic domain. Strain
38
Titin is attached at its C-terminus to M line by a complex formed by obscurin, obscurin-like
protein-1, and myomesin. Obscurin kinase, titin kinase, and myosin light chain kinase belong to the
family of cytoskeletal, autoregulated, and calcium-calmodulin-regulated protein kinases. M band
that is deformed only during contraction is much more compliant than Z disc, and thus is a much
more suitable location for a strain sensor.
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