ABBA regulates plasma-membrane and actin dynamics to promote radial glia extension.
Radial glia play key roles in neuronal migration, axon guidance, and neurogenesis during development of the central nervous system. However, the molecular mechanisms regulating growth and morphology of these extended cells are unknown. We show that ABBA, a novel member of the IRSp53-MIM protein family, is enriched in different types of radial glia. ABBA binds ATP-actin monomers with high affinity and deforms PtdIns(4,5)P(2)-rich membranes in vitro through its WH2 and IM domains, respectively. In radial-glia-like C6-R cells, ABBA localises to the interface between the actin cytoskeleton and plasma membrane, and its depletion by RNAi led to defects in lamellipodial dynamics and process extension. Together, this study identifies ABBA as a novel regulator of actin and plasma membrane dynamics in radial glial cells, and provides evidence that membrane binding and deformation activity is critical for the cellular functions of IRSp53-MIM-ABBA family proteins.
Saarikangas
Juha
J
Program in Cellular Biotechnology, Institute of Biotechnology, University of Helsinki, Finland.
Hakanen
Janne
J
Mattila
Pieta K
PK
Grumet
Martin
M
Salminen
Marjo
M
Lappalainen
Pekka
P
D000199:Actins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D020869:Gene Expression Profiling; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D034741:RNA, Small Interfering; D000255:Adenosine Triphosphate; D020744:rac GTP-Binding Proteins