Septin-driven coordination of actin and microtubule remodeling regulates the collateral branching of axons

Jianli Hu, Xiaobo Bai, Jonathan R. Bowen, Lee Dolat, Farida Korobova, Wenqian Yu, Peter W. Baas, Tatyana Svitkina, Gianluca Gallo*, Elias T. Spiliotis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Axon branching is fundamental to the development of the peripheral and central nervous system [1, 2]. Branches that sprout from the axon shaft are termed collateral or interstitial branches [3, 4]. Collateral branching of axons requires the formation of filopodia from actin microfilaments (F-actin) and their engorgement with microtubules (MTs) that splay from the axon shaft [4-6]. The mechanisms that drive and coordinate the remodeling of actin and MTs during branch morphogenesis are poorly understood. Septins comprise a family of GTP-binding proteins that oligomerize into higher-order structures, which associate with membranes and the actin and microtubule cytoskeleton [7, 8]. Here, we show that collateral branching of axons requires SEPT6 and SEPT7, two interacting septins [9]. In the axons of sensory neurons, both SEPT6 and SEPT7 accumulate at incipient sites of filopodia formation. We show that SEPT6 localizes to axonal patches of F-actin and increases the recruitment of cortactin, a regulator of Arp2/3-mediated actin polymerization, triggering the emergence of filopodia. Conversely, SEPT7 promotes the entry of axonal MTs into filopodia, enabling the formation of collateral branches. Surprisingly, septins provide a novel mechanism for the collateral branching of axons by coordinating the remodeling of the actin and microtubule cytoskeleton.

Original languageEnglish (US)
Pages (from-to)1109-1115
Number of pages7
JournalCurrent Biology
Volume22
Issue number12
DOIs
StatePublished - Jun 19 2012

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry, Genetics and Molecular Biology

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