Critical Role of Collapsin Response Mediator Protein-associated Molecule CRAM for Filopodia and Growth Cone Development in Neurons

Author:

Hotta Azusa1,Inatome Ryoko1,Yuasa-Kawada Junichi1,Qin Qingyu1,Yamamura Hirohei1,Yanagi Shigeru12

Affiliation:

1. Division of Proteomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan

2. Precursory Research for Embryonic Science and Technology, Japanese Science and Technology, Saitama 332, Japan

Abstract

Collapsin response mediator proteins (CRMPs) have been implicated in signaling of axonal guidance, including semaphorins. We have previously identified a unique member of this gene family, CRMP-associated molecule CRAM (CRMP-5), which is phylogenetically divergent from the other four CRMPs. In this study, we have examined the distribution and function of CRAM in developing neurons. Immunohistochemical analysis showed accumulation of CRAM in the filopodia of growth cones. Experiments using cytochalasin D indicated that filopodial localization of CRAM was independent of filamentous actin. Overexpression of CRAM in neuronal cells significantly promoted filopodial growth and led to the formation of supernumerary growth cones, which acquired resistance to semaphorin-3A stimulation. Finally, knockdown of CRAM by using RNA interference blocked filopodial formation and revealed an aberrant morphology of growth cones. We propose that CRAM regulates filopodial dynamics and growth cone development, thereby restricting the response of growth cone to repulsive guidance cues.

Publisher

American Society for Cell Biology (ASCB)

Subject

Cell Biology,Molecular Biology

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