Tropomodulins and tropomyosins: working as a team
#MMPMID23828180
Colpan M
; Moroz NA
; Kostyukova AS
J Muscle Res Cell Motil
2013[Aug]; 34
(3-4
): 247-60
PMID23828180
show ga
Actin filaments are major components of the cytoskeleton in eukaryotic cells and
are involved in vital cellular functions such as cell motility and muscle
contraction. Tmod and TM are crucial constituents of the actin filament network,
making their presence indispensable in living cells. Tropomyosin (TM) is an
alpha-helical, coiled coil protein that covers the grooves of actin filaments and
stabilizes them. Actin filament length is optimized by tropomodulin (Tmod), which
caps the slow growing (pointed end) of thin filaments to inhibit polymerization
or depolymerization. Tmod consists of two structurally distinct regions: the
N-terminal and the C-terminal domains. The N-terminal domain contains two
TM-binding sites and one TM-dependent actin-binding site, whereas the C-terminal
domain contains a TM-independent actin-binding site. Tmod binds to two TM
molecules and at least one actin molecule during capping. The interaction of Tmod
with TM is a key regulatory factor for actin filament organization. The binding
efficacy of Tmod to TM is isoform-dependent. The affinities of Tmod/TM binding
influence the proper localization and capping efficiency of Tmod at the pointed
end of actin filaments in cells. Here we describe how a small difference in the
sequence of the TM-binding sites of Tmod may result in dramatic change in
localization of Tmod in muscle cells or morphology of non-muscle cells. We also
suggest most promising directions to study and elucidate the role of Tmod-TM
interaction in formation and maintenance of sarcomeric and cytoskeletal
structure.
free
free
free
