CD44 regulates dendrite morphogenesis through src tyrosine kinase-dependent positioning of the Golgi

Anna Skupien, Anna Konopka, PaweI Trzaskoma, Josephine Labus, Adam Gorlewicz, Lukasz Swiech, Matylda Babraj, Hubert Dolezyczek, Izabela Figiel, Evgeni Ponimaskin, Jakub Wlodarczyk, Jacek Jaworski, Grzegorz M Wilczynski, Joanna Dzwonek

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The acquisition of proper dendrite morphology is a crucial aspect of neuronal development towards the formation of a functional network. The role of the extracellular matrix and its cellular receptors in this process has remained enigmatic. We report that the CD44 adhesion molecule, the main hyaluronan receptor, is localized in dendrites and plays a crucial inhibitory role in dendritic tree arborization in vitro and in vivo. This novel function is exerted by the activation of Src tyrosine kinase, leading to the alteration of Golgi morphology. The mechanism operates during normal brain development, but its inhibition might have a protective influence on dendritic trees under toxic conditions, during which the silencing of CD44 expression prevents dendritic shortening induced by glutamate exposure. Overall, our results indicate a novel role for CD44 as an essential regulator of dendritic arbor complexity in both health and disease.

Original languageEnglish
Pages (from-to)5038-5051
Number of pages14
JournalJournal of Cell Science
Volume127
Issue number23
DOIs
Publication statusPublished - 1 Dec 2014
Externally publishedYes

Keywords

  • Animals
  • Animals, Newborn
  • Antigens, CD44
  • Cerebral Cortex
  • Dendrites
  • Enzyme Activation
  • Female
  • Focal Adhesion Kinase 1
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Glutamic Acid
  • Golgi Apparatus
  • HEK293 Cells
  • HeLa Cells
  • Hippocampus
  • Humans
  • Male
  • Morphogenesis
  • Mutation
  • Neurogenesis
  • RNA Interference
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Transfection
  • src-Family Kinases
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Src kinase
  • Extracellular matrix
  • Dendritic arborization
  • Golgi fragmentation
  • CD44

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    Skupien, A., Konopka, A., Trzaskoma, P., Labus, J., Gorlewicz, A., Swiech, L., ... Dzwonek, J. (2014). CD44 regulates dendrite morphogenesis through src tyrosine kinase-dependent positioning of the Golgi. Journal of Cell Science, 127(23), 5038-5051. https://doi.org/10.1242/jcs.154542