RRC ID |
67315
|
著者 |
Kawabata Galbraith K, Fujishima K, Mizuno H, Lee SJ, Uemura T, Sakimura K, Mishina M, Watanabe N, Kengaku M.
|
タイトル |
MTSS1 Regulation of Actin-Nucleating Formin DAAM1 in Dendritic Filopodia Determines Final Dendritic Configuration of Purkinje Cells.
|
ジャーナル |
Cell Rep
|
Abstract |
Dendritic filopodia of developing neurons function as environmental sensors, regulating the spatial organization of dendrites and proper targeting to presynaptic partners. Dendritic filopodia morphology is determined by the balance of F-actin assembled via two major nucleating pathways, the ARP2/3 complex and formins. The inverse-BAR protein MTSS1 is highly expressed in Purkinje cells (PCs) and has been shown to upregulate ARP2/3 activity. PCs in MTSS1 conditional knockout mice showed dendrite hypoplasia due to excessive contact-induced retraction during development. This phenotype was concomitant with elongated dendritic filopodia and was phenocopied by overactivation of the actin nucleator formin DAAM1 localized in the tips of PC dendritic protrusions. Cell biology assays including single-molecule speckle microscopy demonstrated that MTSS1's C terminus binds to DAAM1 and paused DAAM1-mediated F-actin polymerization. Thus, MTSS1 plays a dual role as a formin inhibitor and ARP2/3 activator in dendritic filopodia, determining final neuronal morphology.
|
巻・号 |
24(1)
|
ページ |
95-106.e9
|
公開日 |
2018-7-3
|
DOI |
10.1016/j.celrep.2018.06.013
|
PII |
S2211-1247(18)30908-2
|
PMID |
29972794
|
MeSH |
Actins / metabolism
Animals
Dendrites / metabolism*
Dendritic Spines / metabolism
HEK293 Cells
Humans
Mice
Mice, Knockout
Microfilament Proteins / deficiency
Microfilament Proteins / metabolism*
NIH 3T3 Cells
Neoplasm Proteins / deficiency
Neoplasm Proteins / metabolism*
Protein Binding
Pseudopodia / metabolism*
Purkinje Cells / metabolism*
rho GTP-Binding Proteins / metabolism*
|
IF |
8.109
|
リソース情報 |
ヒト・動物細胞 |
293T(RCB2202)
NIH3T3-3-4(RCB1862) |