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Arl13b and the non-muscle myosin heavy chain IIA are required for circular dorsal ruffle formation and cell migration
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Resumo(s)
The Arf-like protein Arl13b has been implicated in ciliogenesis and Sonic hedgehog signaling. Furthermore, we have previously shown that it regulates endocytic recycling traffic and interacts with actin. Herein, we report that the non-muscle myosin heavy chain IIA, also known as Myh9, is an Arl13b effector. Moreover, we found that both proteins localized to circular dorsal ruffles (CDRs) induced by platelet-derived growth factor stimulation and are required for their formation. CDRs are ring-shaped actin-dependent structures formed on the dorsal cell surface and are involved in diverse processes, such as macropinocytosis, integrin recycling, internalization of receptor tyrosine kinases and cell migration. We found that Arl13b or Myh9 silencing impaired cell migration, suggesting that Arl13b is required for this function through the interaction with Myh9. Moreover, Arl13b silencing impaired neural crest cell migration in zebrafish embryos. Furthermore, we showed that Arl13b is required for the formation of CDRs in migrating cells. Thus, our results indicate a new role for Arl13b in actin cytoskeleton remodeling through the interaction with Myh9, by driving the formation of CDRs necessary for cell migration.
Descrição
This work was supported by a Marie Curie International Reintegration Grant [grant number Marie Curie_PIRG05-GA-2009-247726 to D.C.B.]; by postdoctoral fellowships from Fundacao para a Ciencia e Tecnologia (FCT) [grant numbers SFRH/BPD/78561/2011 to C.C., SFRH/BPD/32323/2006 to C.S.]; a PhD fellowship from FCT [grant number SFRH/BD/68502/2010 to A.P.]; and a FCT grant [grant number PTDC/SAU-OBD/103981/2008 to S.L.].
Palavras-chave
Actin cytoskeleton LOCALIZATION Arl13b PROTEINS Wound healing MACROPINOCYTOSIS Circular dorsal ruffle Small G protein ZEBRAFISH Platelet-derived growth factor signaling PRIMARY CILIA Myosin heavy chain IIA ACTIN Myh9 LEAD JOUBERT-SYNDROME RECEPTOR ROLES Arl13b Myosin heavy chain IIA Myh9 Circular dorsal ruffle Small G protein Actin cytoskeleton Platelet-derived growth factor signaling Wound healing