The role of a LAR-like receptor tyrosine phosphatase in growth cone collapse and mutual-avoidance by sibling processes

Baker, Maureen; Macagno, Eduardo R.

doi:10.1002/1097-4695(200008)44:2<194::aid-neu9>3.0.co;2-j

Cited by 18 publications

(7 citation statements)

References 50 publications

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“…Thus, other classically defined homophilic adhesion proteins that are characterized by their ability to mediate aggregation in cultured cells in vitro may act in vivo to promote repulsion. Indeed, two other homophilic proteins, the protocadherin Flamingo in Drosophila (Lee et al 2003, Usui et al 1999) and the Lar phosphatase in the leech (Baker & Macagno 2000), which promote aggregation in vitro, have been proposed to mediate homophilic repulsion in vivo. These studies underscore the importance of both gain-and lossof-function studies in different developmental contexts to explore the mechanisms by which homophilic binding between proteins on opposing cellular processes mediates neural circuit assembly.…”

Section: Repulsive Interactions Between Other Homophilic Molecules Mamentioning

confidence: 99%

Dscam-Mediated Cell Recognition Regulates Neural Circuit Formation

Hattori

Millard

Wojtowicz

et al. 2008

Annu. Rev. Cell Dev. Biol.

193

158

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The Dscam family of immunoglobulin cell surface proteins mediates recognition events between neurons that play an essential role in the establishment of neural circuits. The Drosophila Dscam1 locus encodes tens of thousands of cell surface proteins via alternative splicing. These isoforms exhibit exquisite isoform-specific binding in vitro that mediates homophilic repulsion in vivo. These properties provide the molecular basis for self-avoidance, an essential developmental mechanism that allows axonal and dendritic processes to uniformly cover their synaptic fields. In a mechanistically similar fashion, homophilic repulsion mediated by Drosophila Dscam2 prevents processes from the same class of cells from occupying overlapping synaptic fields through a process called tiling. Genetic studies in the mouse visual system support the view that vertebrate DSCAM also promotes both self-avoidance and tiling. By contrast, DSCAM and DSCAM-L promote layerspecific targeting in the chick visual system, presumably through promoting homophilic adhesion. The fly and mouse studies underscore the importance of homophilic repulsion in regulating neural circuit assembly, whereas the chick studies suggest that DSCA Mproteins may mediate a variety of different recognition events during wiring in a context-dependent fashion.

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Section: Repulsive Interactions Between Other Homophilic Molecules Mamentioning

confidence: 99%

Dscam-Mediated Cell Recognition Regulates Neural Circuit Formation

Hattori

Millard

Wojtowicz

et al. 2008

Annu. Rev. Cell Dev. Biol.

193

158

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“…Recent invertebrate studies have identified a number of cell-surface molecules that are required cell-autonomously for establishing non-overlapping dendrites or axons in a roughly two dimensional (2D) plane. They include the Down’s syndrome cell adhesion molecule (Dscam) (Hughes et al, 2007; Matthews et al, 2007; Soba et al, 2007), the secreted guidance molecule Netrin and its receptors (Smith et al, 2012), the cadherin member Flamingo (Fmi) (Matsubara et al, 2011), the Leukocyte Antigen Related (LAR) protein receptor tyrosine phosphatase (Baker and Macagno, 2000), the cell adhesion molecule integrin (Han et al, 2012; Kim et al, 2012), and the tripartite ligand-receptor complex involving SAX-7, MNR-1, and DMA-1 (Dong et al, 2013; Salzberg et al, 2013). In mammals, however, only a few molecules, including Dscam and the related DscamL1 (Fuerst et al, 2009), the transmembrane semaphorin 6A (Sema6A) (Matsuoka et al, 2012), and the gamma cluster of protocadherins (Pcdhgs) (Lefebvre et al, 2012), have been studied for their self-avoidance function in subpopulations of retinal cells and cerebellar Purkinje cells (PCs).…”

Section: Introductionmentioning

confidence: 99%

Dendrite Self-Avoidance Requires Cell-Autonomous Slit/Robo Signaling in Cerebellar Purkinje Cells

Gibson

Tymanskyj

Yuan

et al. 2014

Neuron

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SUMMARY Dendrites from the same neuron usually develop non-overlapping patterns by self-avoidance, a process requiring contact-dependent recognition and repulsion. Recent studies have implicated homophilic interactions of cell surface molecules, including Dscams and Pcdhgs, in self-recognition, but repulsive molecular mechanisms remain obscure. Here we report a new role for the secreted molecule Slit2 and its receptor Robo2 in self-avoidance of cerebellar Purkinje cells (PCs). Both molecules are highly expressed by PCs, and their deletion leads to excessive dendrite self-crossing without affecting arbor size and shape. This cell-autonomous function is supported by the boundary-establishing activity of Slit in culture and the phenotype rescue by membrane-associated Slit2 activities. Furthermore, genetic studies show that they act independently from Pcdhg-mediated recognition. Finally, PC-specific deletion of Robo2 is associated with motor behavior alterations. Thus, our study uncovers a local repulsive mechanism required for self-avoidance and demonstrates the molecular complexity at the cell surface in dendritic patterning.

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“…Analyses of Drosophila mutants lacking LAR suggest a role for LAR in regulation of motor axon defasciculation (Krueger et al ., 1996), target recognition by retinal neurons (Clandinin et al ., 2001; Maurel‐Zaffran et al ., 2001) and synapse morphogenesis (Kaufmann et al ., 2002). In leech neural development, inhibition of HmLAR2 (an ortholog of LAR) function leads to shortened and aberrant neuronal projections, navigational crossover errors and growth cone collapse (Gershon et al ., 1998; Baker & Macagno, 2000; Baker et al. , 2000).…”

Section: Introductionmentioning

confidence: 99%

Identification of an ectodomain within the LAR protein tyrosine phosphatase receptor that binds homophilically and activates signalling pathways promoting neurite outgrowth

Yang

Yin

Derevyanny

et al. 2005

Eur J of Neuroscience

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Elucidation of mechanisms by which receptor protein tyrosine phosphatases (PTPs) regulate neurite outgrowth will require characterization of ligand-receptor interactions and identification of ligand-induced signalling components mediating neurite outgrowth. The first identified ligand of the leucocyte common antigen-related (LAR) receptor PTP consists of a 99-residue ectodomain isoform, termed LARFN5C, which undergoes homophilic binding to LAR and promotes neurite outgrowth. We employed peptide mapping of LARFN5C to identify an active neurite-promoting domain of LAR. A peptide mimetic consisting of 37 residues (L59) and corresponding to the fifth LAR fibronectin type III (FNIII) domain prevented LARFN5C homophilic binding, demonstrated homophilic binding to itself and promoted neurite outgrowth of mouse E16-17 hippocampal neurons and of dorsal root ganglia explants. Response to L59 was partially lost when using neurons derived from LAR-deficient (-/-) mice or neurons treated with LAR siRNA, consistent with homophilic interaction of L59 with LAR. L59 neurite-promoting activity was decreased in the presence of inhibitors of Src, Trk, PLCgamma, PKC, PI3K and MAPK. L59 activated Src (a known substrate of LAR), FAK and TrkB and also activated downstream signalling intermediates including PKC, ERK, AKT and CREB. BDNF augmented the maximal neurite-promoting activity of L59, a finding consistent with the presence of shared and distinct signalling pathways activated by L59 with BDNF and L59 with TrkB. These studies are the first to identify an ectodomain of LAR (located within the fifth FNIII domain) capable of promoting neurite outgrowth and point to novel approaches for promotion of neurite outgrowth.

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The role of a LAR-like receptor tyrosine phosphatase in growth cone collapse and mutual-avoidance by sibling processes

Cited by 18 publications

References 50 publications

Dscam-Mediated Cell Recognition Regulates Neural Circuit Formation

Dscam-Mediated Cell Recognition Regulates Neural Circuit Formation

Dendrite Self-Avoidance Requires Cell-Autonomous Slit/Robo Signaling in Cerebellar Purkinje Cells

Identification of an ectodomain within the LAR protein tyrosine phosphatase receptor that binds homophilically and activates signalling pathways promoting neurite outgrowth

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