Arl13b and the non-muscle myosin heavy chain IIA are required for circular dorsal ruffle formation and cell migration.
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.
CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
Cristina
C
Casalou
CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
Cecília
C
Seixas
CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
Ana
A
Portelinha
CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
Petra
P
Pintado
CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
Mafalda
M
Barros
CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
José S
JS
Ramalho
CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal.
Susana S
SS
Lopes
CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal duarte.barral@fcm.unl.pt.
Duarte C
DC
Barral
D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D022081:Cell Surface Extensions / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018995:Myosin Heavy Chains; D041681:NIH 3T3 Cells; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D010873:Pinocytosis; D021381:Protein Transport; D015027:Zebrafish
C560093:Arl13b protein, mouse; C525088:Myh9 protein, mouse; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains; D020727:ADP-Ribosylation Factors
Actin cytoskeleton; Arl13b; Circular dorsal ruffle; Myh9; Myosin heavy chain IIA; Platelet-derived growth factor signaling; Small G protein; Wound healing