The receptor phosphatase HmLAR2 collaborates with focal adhesion proteins in filopodial tips to control growth cone morphology

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Abstract

Receptor protein tyrosine phosphatases (RPTPs) have been shown to play key roles in regulating axon guidance and synaptogenesis. HmLAR2, one of two closely related LAR-like RPTPs in the embryonic leech, is expressed in a few central neurons and in a unique segmentally-iterated peripheral cell, the comb cell (CC). Here we show that tagged HmLAR2-EGFP has a punctate pattern of expression in the growth cones of the CC, particularly at the tips of extending filopodia. Moreover, although expression of the wild-type EGFP-tagged receptor does not affect CC growth cone morphology, expression of a putative dominant-negative mutant of the receptor, CS-HmLAR2, leads to the enlargement of the growth cones, a shortening of filopodia, and errors in cellular tiling. RNAi of several candidate substrate signaling proteins, Lena (leech Ena/Vasp), β-integrin and paxillin, but not β-catenin, phenocopies particular aspects of the effects of HmLAR2 RNAi. For paxillin, which co-localizes with HmLAR2 at growth cone puncta, knock-down led to a reduction in the number of such puncta. Together, our data suggests that HmLAR2 regulates the morphology of the growth cone by controlling F-actin polymerization and focal adhesion complexes. © 2008 Elsevier Inc. All rights reserved.

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Baker, M. W., Peterson, S. M., & Macagno, E. R. (2008). The receptor phosphatase HmLAR2 collaborates with focal adhesion proteins in filopodial tips to control growth cone morphology. Developmental Biology, 320(1), 215–225. https://doi.org/10.1016/j.ydbio.2008.05.522

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