Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane

Schmidt, Nadine; Basu, Sreya; Sladecek, Stefan; Gatti, Sabrina; Haren, Jeffrey van; Treves, Susan; Pielage, Jan; Galjart, Niels; Brenner, Hans Rudolf

doi:10.1083/jcb.201111130

Cited by 59 publications

(102 citation statements)

References 51 publications

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“…LL5b, CLASPs and ELKS were also shown to concentrate at podosomes, actin-rich structures, which can remodel the extracellular matrix (Proszynski and Sanes, 2013). Interestingly, LL5b-containing podosome-like structures are also formed at neuromuscular junctions (Kishi et al, 2005;Proszynski et al, 2009;Proszynski and Sanes, 2013), and the complexes of LL5b and CLASPs were shown to capture microtubule plus ends and promote delivery of acetylcholine receptors (Basu et al, 2015(Basu et al, , 2014Schmidt et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

Bouchet

Gough

Willige

et al. 2016

Preprint

108

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The cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix plays a crucial role in cell polarity and migration. Microtubules regulate the turnover of adhesion sites, and, in turn, focal adhesions promote the cortical microtubule capture and stabilization in their vicinity, but the underlying mechanism is unknown. Here, we show that cortical microtubule stabilization sites containing CLASPs, KIF21A, LL5b and liprins are recruited to focal adhesions by the adaptor protein KANK1, which directly interacts with the major adhesion component, talin. Structural studies showed that the conserved KN domain in KANK1 binds to the talin rod domain R7. Perturbation of this interaction, including a single point mutation in talin, which disrupts KANK1 binding but not the talin function in adhesion, abrogates the association of microtubule-stabilizing complexes with focal adhesions. We propose that the talin-KANK1 interaction links the two macromolecular assemblies that control cortical attachment of actin fibers and microtubules.

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Section: Introductionmentioning

confidence: 99%

Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

Bouchet

Gough

Willige

et al. 2016

Preprint

108

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“…The CLASPs (CLASP1 and CLASP2), discovered in 2001 as binding partners for the CAP-Gly domain-containing linker proteins 1 and 2 (CLIP1/CLIP-170 and CLIP2/CLIP-115), were initially found to bind and stabilize the growing, distal ends of microtubules, independently of the CLIPs (17). Subsequent studies revealed that CLASPs localize wherever microtubules are needed, kinetochores in the nucleus for mitosis (18)(19)(20)(21)(22)(23), the cell cortex (24-27), the leading edge lamella and lamellipodium of motile cells (28)(29)(30)(31), the Golgi (17,(32)(33)(34)(35)(36)(37)(38), axons (39, 40), the developing apical membrane surface during lumen formation within endothelial cells (41), adherens junctions at cell-cell contacts (42, 43), the neuromuscular junction (44)(45)(46), podosomes (47), and focal adhesions (48). Within each of these molecular systems, the dynamic instability of microtubules undergo differential regulation by proteins specific to each of the biological processes (49)(50)(51)(52)(53)(54)(55).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the CLASP2 Protein Interaction Network Identifies SOGA1 as a Microtubule-Associated Protein

Kruse

Krantz

Barker

et al. 2017

Molecular & Cellular Proteomics

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SummaryCLASP2 is a microtubule-associated protein that undergoes insulin-stimulated phosphorylation and co-localization with reorganized actin and GLUT4 at the plasma membrane.To gain insight to the role of CLASP2 in this system, we developed and successfully executed a streamlined interactome approach and built a CLASP2 protein network in 3T3-L1 adipocytes.Using two different commercially available antibodies for CLASP2 and an antibody for epitopetagged, overexpressed CLASP2, we performed multiple affinity purification coupled with mass spectrometry (AP-MS) experiments in combination with label-free quantitative proteomics and analyzed the data with the bioinformatics tool Significance Analysis of Interactome (SAINT). We discovered that CLASP2 co-immunoprecipitates (co-IPs) the novel protein SOGA1, the microtubule-associated protein kinase MARK2, and the microtubule/actin-regulating protein G2L1. The GTPase-activating proteins AGAP1 and AGAP3 were also enriched in the CLASP2 interactome, although subsequent AGAP3 and CLIP2 interactome analysis suggests a preference of AGAP3 for CLIP2. Follow-up MARK2 interactome analysis confirmed reciprocal co-IP of CLASP2 and also revealed MARK2 can co-IP SOGA1, glycogen synthase, and glycogenin.Investigating the SOGA1 interactome confirmed SOGA1 can reciprocal co-IP both CLASP2 and MARK2 as well as glycogen synthase and glycogenin. SOGA1 was confirmed to colocalize with CLASP2 and also with tubulin, which identifies SOGA1 as a new microtubule-associated protein.These results introduce the metabolic function of these proposed novel protein networks and their relationship with microtubules as new fields of cytoskeleton-associated protein biology. 5

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“…CLIP1 was also shown to be involved in the maintenance of a normal neuromuscular phenotype. 26 The N-terminal region of CLIP1 interacts with EB1 and alphatubulin, leading to CLIP1 localization on MT plus ends. 27 CLIP1 also interacts with IQGAP1 (IQ Motif Containing GTPase Activating Protein 1), which together with CLIP1, is part of a complex that has a role in linking the actin cytoskeleton to MTs during cell migration.…”

Section: Discussionmentioning

confidence: 99%

A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability

Larti¹,

Kahrizi²,

Musante³

et al. 2014

Eur J Hum Genet

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In the context of a comprehensive research project, investigating novel autosomal recessive intellectual disability (ARID) genes, linkage analysis based on autozygosity mapping helped identify an intellectual disability locus on Chr.12q24, in an Iranian family (LOD score ¼ 3.7). Next-generation sequencing (NGS) following exon enrichment in this novel interval, detected a nonsense mutation (p.Q1010*) in the CLIP1 gene. CLIP1 encodes a member of microtubule (MT) plus-end tracking proteins, which specifically associates with the ends of growing MTs. These proteins regulate MT dynamic behavior and are important for MT-mediated transport over the length of axons and dendrites. As such, CLIP1 may have a role in neuronal development. We studied lymphoblastoid and skin fibroblast cell lines established from healthy and affected patients. RT-PCR and western blot analyses showed the absence of CLIP1 transcript and protein in lymphoblastoid cells derived from affected patients. Furthermore, immunofluorescence analyses showed MT plus-end staining only in fibroblasts containing the wild-type (and not the mutant) CLIP1 protein. Collectively, our data suggest that defects in CLIP1 may lead to ARID.

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Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane

Abstract: Agrin regulates acetylcholine receptors at the neuromuscular junction by locally stabilizing microtubules through the plus end tracking proteins CLASP2 and CLIP-170.

Cited by 59 publications

References 51 publications

Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

Characterization of the CLASP2 Protein Interaction Network Identifies SOGA1 as a Microtubule-Associated Protein

A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability

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