The TOCA family of F-BAR–containing proteins bind to and remodel lipid bilayers via their conserved F-BAR domains, and regulate actin dynamics via their N-Wasp binding SH3 domains. Thus, these proteins are predicted to play a pivotal role in coordinating membrane traffic with actin dynamics during cell migration and tissue morphogenesis. By combining genetic analysis in Caenorhabditis elegans with cellular biochemical experiments in mammalian cells, we showed that: i) loss of CeTOCA proteins reduced the efficiency of Clathrin-mediated endocytosis (CME) in oocytes. Genetic interference with CeTOCAs interacting proteins WSP-1 and WVE-1, and other components of the WVE-1 complex, produced a similar effect. Oocyte endocytosis defects correlated well with reduced egg production in these mutants. ii) CeTOCA proteins localize to cell–cell junctions and are required for proper embryonic morphogenesis, to position hypodermal cells and to organize junctional actin and the junction-associated protein AJM-1. iii) Double mutant analysis indicated that the toca genes act in the same pathway as the nematode homologue of N-WASP/WASP, wsp-1. Furthermore, mammalian TOCA-1 and C. elegans CeTOCAs physically associated with N-WASP and WSP-1 directly, or WAVE2 indirectly via ABI-1. Thus, we propose that TOCA proteins control tissues morphogenesis by coordinating Clathrin-dependent membrane trafficking with WAVE and NWASP– dependent actin-dynamics

Requirements for F-BAR proteins TOCA-1 and TOCA-2 in actin dynamics and membrane trafficking during caenorhabditis elegans oocyte growth and embryonic epidermal morphogenesis / C. Giuliani, F. Troglio, Z. Bai, F.B. Patel, A. Zucconi1, M.G. Malabarba, A. Disanza, T.B. Stradal, G. Cassata, S. Confalonieri, J.D. Hardin, M.C. Soto, B.D. Grant, G. Scita. - In: PLOS GENETICS. - ISSN 1553-7390. - 5:10(2009 Oct), p. e1000675.e1000675.

Requirements for F-BAR proteins TOCA-1 and TOCA-2 in actin dynamics and membrane trafficking during caenorhabditis elegans oocyte growth and embryonic epidermal morphogenesis

M.G. Malabarba;G. Scita
Ultimo
2009

Abstract

The TOCA family of F-BAR–containing proteins bind to and remodel lipid bilayers via their conserved F-BAR domains, and regulate actin dynamics via their N-Wasp binding SH3 domains. Thus, these proteins are predicted to play a pivotal role in coordinating membrane traffic with actin dynamics during cell migration and tissue morphogenesis. By combining genetic analysis in Caenorhabditis elegans with cellular biochemical experiments in mammalian cells, we showed that: i) loss of CeTOCA proteins reduced the efficiency of Clathrin-mediated endocytosis (CME) in oocytes. Genetic interference with CeTOCAs interacting proteins WSP-1 and WVE-1, and other components of the WVE-1 complex, produced a similar effect. Oocyte endocytosis defects correlated well with reduced egg production in these mutants. ii) CeTOCA proteins localize to cell–cell junctions and are required for proper embryonic morphogenesis, to position hypodermal cells and to organize junctional actin and the junction-associated protein AJM-1. iii) Double mutant analysis indicated that the toca genes act in the same pathway as the nematode homologue of N-WASP/WASP, wsp-1. Furthermore, mammalian TOCA-1 and C. elegans CeTOCAs physically associated with N-WASP and WSP-1 directly, or WAVE2 indirectly via ABI-1. Thus, we propose that TOCA proteins control tissues morphogenesis by coordinating Clathrin-dependent membrane trafficking with WAVE and NWASP– dependent actin-dynamics
Settore MED/04 - Patologia Generale
ott-2009
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000675
Article (author)
File in questo prodotto:
File Dimensione Formato  
journal.pgen.1000675[1].pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 706.29 kB
Formato Adobe PDF
706.29 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/71812
Citazioni
  • ???jsp.display-item.citation.pmc??? 36
  • Scopus 52
  • ???jsp.display-item.citation.isi??? 45
social impact