TY - JOUR
T1 - Tropomyosins Regulate the Severing Activity of Gelsolin in Isoform-Dependent and Independent Manners
AU - Kis-Bicskei, Nikolett
AU - Bécsi, Bálint
AU - Erdődi, Ferenc
AU - Robinson, Robert C.
AU - Bugyi, Beáta
AU - Huber, Tamás
AU - Nyitrai, Miklós
AU - Talián, Gábor Csaba
N1 - Funding Information:
This work was supported by grants from the National Research, Development and Innovation Office and the European Union ( GINOP-2.3.3-15-2016-00025 , GINOP-2.3.2-15-2016-00049 , and EFOP-3.6.1-16-2016-00004 ) and by the Hungarian Science Foundation ( OTKA grants K112794 to M.N., K109689 to B.B., and K109249 to F.E.). This research was supported in addition by the European Union and the State of Hungary , co-financed by the European Social Fund in the framework of TÁMOP 4.2.4.A/2-11-1-2012-0001 “National Excellence Program” and the New National Excellence Program of the Ministry of Human Capacities (to B.B. and T.H.), and by the ÚNKP-16-4 and ÚNKP-17-4 New National Excellence Program of the Ministry of Human Capacities (to B.B.). R.C.R. was supported by the Biomedical Research Council , Agency for Science , Technology and Research ( A ∗ STAR ), Singapore.
Publisher Copyright:
© 2018 Biophysical Society
PY - 2018/2/27
Y1 - 2018/2/27
N2 - The actin cytoskeleton fulfills numerous key cellular functions, which are tightly regulated in activity, localization, and temporal patterning by actin binding proteins. Tropomyosins and gelsolin are two such filament-regulating proteins. Here, we investigate how the effects of tropomyosins are coupled to the binding and activity of gelsolin. We show that the three investigated tropomyosin isoforms (Tpm1.1, Tpm1.12, and Tpm3.1) bind to gelsolin with micromolar or submicromolar affinities. Tropomyosin binding enhances the activity of gelsolin in actin polymerization and depolymerization assays. However, the effects of the three tropomyosin isoforms varied. The tropomyosin isoforms studied also differed in their ability to protect pre-existing actin filaments from severing by gelsolin. Based on the observed specificity of the interactions between tropomyosins, actin filaments, and gelsolin, we propose that tropomyosin isoforms specify which populations of actin filaments should be targeted by, or protected from, gelsolin-mediated depolymerization in living cells.
AB - The actin cytoskeleton fulfills numerous key cellular functions, which are tightly regulated in activity, localization, and temporal patterning by actin binding proteins. Tropomyosins and gelsolin are two such filament-regulating proteins. Here, we investigate how the effects of tropomyosins are coupled to the binding and activity of gelsolin. We show that the three investigated tropomyosin isoforms (Tpm1.1, Tpm1.12, and Tpm3.1) bind to gelsolin with micromolar or submicromolar affinities. Tropomyosin binding enhances the activity of gelsolin in actin polymerization and depolymerization assays. However, the effects of the three tropomyosin isoforms varied. The tropomyosin isoforms studied also differed in their ability to protect pre-existing actin filaments from severing by gelsolin. Based on the observed specificity of the interactions between tropomyosins, actin filaments, and gelsolin, we propose that tropomyosin isoforms specify which populations of actin filaments should be targeted by, or protected from, gelsolin-mediated depolymerization in living cells.
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U2 - 10.1016/j.bpj.2017.11.3812
DO - 10.1016/j.bpj.2017.11.3812
M3 - Article
C2 - 29490240
AN - SCOPUS:85042629304
SN - 0006-3495
VL - 114
SP - 777
EP - 787
JO - Biophysical Journal
JF - Biophysical Journal
IS - 4
ER -