Septin-Driven Coordination of Actin and Microtubule Remodeling Regulates the Collateral Branching of Axons

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

doi:10.1016/j.cub.2012.04.019

Cited by 144 publications

(154 citation statements)

References 32 publications

(46 reference statements)

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“…14). Under basal branching conditions F-actin is enriched at the tip of the leading process and is arranged in a highly branched network created by cortactin, which along with Arp2/3 is known to promote branch growth in neurons (Mingorance-Le Meur and O'Connor, 2009;Spillane et al, 2011;Hu et al, 2012). Microtubule invasion changes growing actin protrusions to stable branches.…”

Section: Discussionmentioning

confidence: 99%

SDF1 Reduces Interneuron Leading Process Branching through Dual Regulation of Actin and Microtubules

2014

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Normal cerebral cortical function requires a highly ordered balance between projection neurons and interneurons. During development these two neuronal populations migrate from distinct progenitor zones to form the cerebral cortex, with interneurons originating in the more distant ganglionic eminences. Moreover, deficits in interneurons have been linked to a variety of neurodevelopmental disorders underscoring the importance of understanding interneuron development and function. We, and others, have identified SDF1 signaling as one important modulator of interneuron migration speed and leading process branching behavior in mice, although how SDF1 signaling impacts these behaviors remains unknown. We previously found SDF1 inhibited leading process branching while increasing the rate of migration. We have now mechanistically linked SDF1 modulation of leading process branching behavior to a dual regulation of both actin and microtubule organization. We find SDF1 consolidates actin at the leading process tip by de-repressing calpain protease and increasing proteolysis of branched-actin-supporting cortactin. Additionally, SDF1 stabilizes the microtubule array in the leading process through activation of the microtubule-associated protein doublecortin (DCX). DCX stabilizes the microtubule array by bundling microtubules within the leading process, reducing branching. These data provide mechanistic insight into the regulation of interneuron leading process dynamics during neuronal migration in mice and provides insight into how cortactin and DCX, a known human neuronal migration disorder gene, participate in this process.

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Section: Discussionmentioning

confidence: 99%

SDF1 Reduces Interneuron Leading Process Branching through Dual Regulation of Actin and Microtubules

2014

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“…Septin 7 interacts with nephrin and CD2-associated protein (CD2AP) (Wasik et al, 2012), both of which are expressed in podocytes and are essential for kidney ultrafiltration function (Kestilä et al, 1998;Shih et al, 1999). In cultured hippocampal neurons, septin 7 regulates dendritic branching and the morphology of dendritic spines during neuronal maturation (Hu et al, 2012;Tada et al, 2007;Xie et al, 2007). Despite the apparent importance of the expression of septin 7 in various cell types, little is known about its function in vivo.…”

Section: Introductionmentioning

confidence: 99%

sept7b is essential for pronephric function and development of left–right asymmetry in zebrafish embryogenesis

Dash¹,

Lehtonen²,

Wasik³

et al. 2014

Development

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The conserved septin family of filamentous small GTPases plays important roles in mitosis, cell migration and cell morphogenesis by forming scaffolds and diffusion barriers. Recent studies in cultured cells in vitro indicate that a septin complex of septin 2, 7 and 9 is required for ciliogenesis and cilia function, but septin function in ciliogenesis in vertebrate organs in vivo is not understood. We show that sept7b is expressed in ciliated cells in different tissues during early zebrafish development. Knockdown of sept7b by using morpholino antisense oligonucleotides caused misorientation of basal bodies and cilia, reduction of apical actin and the shortening of motile cilia in Kupffer's vesicle and pronephric tubules. This resulted in pericardial and yolk sac edema, body axis curvature and hydrocephaly. Notably, in sept7b morphants we detected strong leftright asymmetry defects in the heart and lateral plate mesoderm (situs inversus), reduced fluid flow in the kidney, the formation of kidney cysts and loss of glomerular filtration barrier function. Thus, sept7b is essential during zebrafish development for pronephric function and ciliogenesis, and loss of expression of sept7b results in defects that resemble human ciliopathies.

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“…2006; Hu et al. 2012; ]) per length unit in WT and WIP −/− neurons. WIP −/− neurons had almost twice as many neuritic filopodia as controls (Fig.…”

Section: Resultsmentioning

confidence: 99%

Neuritic complexity of hippocampal neurons depends on WIP‐mediated mTORC1 and Abl family kinases activities

Franco-Villanueva

Antón

2015

Brain and Behavior

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IntroductionNeuronal morphogenesis is governed mainly by two interconnected processes, cytoskeletal reorganization, and signal transduction. The actin‐binding molecule WIP (Wiskott‐Aldrich syndrome protein [WASP]‐interacting protein) was identified as a negative regulator of neuritogenesis. Although WIP controls activity of the actin‐nucleation‐promoting factor neural WASP (N‐WASP) during neuritic differentiation, its implication in signal transduction remains unknown.MethodsUsing primary neurons from WIP‐deficient and wild‐type mice we did an immunofluorescence, morphometric, and biochemical analysis of the signaling modified by WIP deficiency.ResultsHere, we describe the WIP contribution to the regulation of neuritic elaboration and ramification through modification in phosphorylation levels of several kinases that participate in the mammalian target of rapamycin complex 1 (mTORC1)‐p70S6K (phosphoprotein 70 ribosomal protein S6 kinase, S6K) intracellular signaling pathway. WIP deficiency induces an increase in the number of neuritic bifurcations and filopodial protrusions in primary embryonic neurons. This phenotype is not due to modifications in the activity of the phosphoinositide 3 kinase (PI3K)‐Akt pathway, but to reduced phosphorylation of the S6K residues Ser411 and Thr389. The resulting decrease in kinase activity leads to reduced S6 phosphorylation in the absence of WIP. Incubation of control neurons with pharmacological inhibitors of mTORC1 or Abl, two S6K regulators, conferred a morphology resembling that of WIP‐deficient neurons. Moreover, the preferential co‐distribution of phospho‐S6K with polymerized actin is altered in WIP‐deficient neurons.ConclusionThese experiments identify WIP as a member of a signaling cascade comprised of Abl family kinases, mTORC1 and S6K, which regulates neuron development and specifically, neuritic branching and complexity. Thus, we postulated a new role for WIP protein.

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Septin-Driven Coordination of Actin and Microtubule Remodeling Regulates the Collateral Branching of Axons

Cited by 144 publications

References 32 publications

SDF1 Reduces Interneuron Leading Process Branching through Dual Regulation of Actin and Microtubules

SDF1 Reduces Interneuron Leading Process Branching through Dual Regulation of Actin and Microtubules

sept7b is essential for pronephric function and development of left–right asymmetry in zebrafish embryogenesis

Neuritic complexity of hippocampal neurons depends on WIP‐mediated mTORC1 and Abl family kinases activities

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