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 language | English |
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Pages (from-to) | 5038-5051 |
Number of pages | 14 |
Journal | Journal of Cell Science |
Volume | 127 |
Issue number | 23 |
DOIs | |
Publication status | Published - 1 Dec 2014 |
Externally published | Yes |
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