Specification of actin filament function and molecular composition by tropomyosin isoforms.
The specific functions of greater than 40 vertebrate nonmuscle tropomyosins (Tms) are poorly understood. In this article we have tested the ability of two Tm isoforms, TmBr3 and the human homologue of Tm5 (hTM5(NM1)), to regulate actin filament function. We found that these Tms can differentially alter actin filament organization, cell size, and shape. hTm5(NM1) was able to recruit myosin II into stress fibers, which resulted in decreased lamellipodia and cellular migration. In contrast, TmBr3 transfection induced lamellipodial formation, increased cellular migration, and reduced stress fibers. Based on coimmunoprecipitation and colocalization studies, TmBr3 appeared to be associated with actin-depolymerizing factor/cofilin (ADF)-bound actin filaments. Additionally, the Tms can specifically regulate the incorporation of other Tms into actin filaments, suggesting that selective dimerization may also be involved in the control of actin filament organization. We conclude that Tm isoforms can be used to specify the functional properties and molecular composition of actin filaments and that spatial segregation of isoforms may lead to localized specialization of actin filament function.
Bryce
Nicole S
NS
Oncology Research Unit, Department of Paediatrics and Child Health, University of Sydney, The Children's Hospital at Westmead, Australia.
Schevzov
Galina
G
Ferguson
Vicki
V
Percival
Justin M
JM
Lin
Jim J-C
JJ
Matsumura
Fumio
F
Bamburg
James R
JR
Jeffrey
Peter L
PL
Hardeman
Edna C
EC
Gunning
Peter
P
Weinberger
Ron P
RP
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D048429:Cell Size; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D024462:Myosin Type II / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D051381:Rats; D022502:Stress Fibers / Q000378:metabolism; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D020033:Protein Isoforms; C498783:TPM3 protein, human; C411923:Tpm3 protein, mouse; C498784:Tpm3 protein, rat; D014335:Tropomyosin; D024462:Myosin Type II