title: CD44 regulates dendrite morphogenesis through Src tyrosine kinase-dependent positioning of the Golgi.
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.
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Skupien
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Konopka
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: PaweI
authors.initials: P
authors.lastname: Trzaskoma
authors.affiliation: Cellular Neurophysiology, Center of Physiology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Josephine
authors.initials: J
authors.lastname: Labus
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Gorlewicz
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Trojdena 4, 02-190 Warsaw, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Swiech
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Matylda
authors.initials: M
authors.lastname: Babraj
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Hubert
authors.initials: H
authors.lastname: Dolezyczek
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Figiel
authors.affiliation: Cellular Neurophysiology, Center of Physiology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Evgeni
authors.initials: E
authors.lastname: Ponimaskin
authors.affiliation: Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Wlodarczyk
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Trojdena 4, 02-190 Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland.
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Wilczynski
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland j.dzwonek@nencki.gov.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Dzwonek
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development / Q000276:immunology; D003712:Dendrites / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D004789:Enzyme Activation; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018698:Glutamic Acid / Q000633:toxicity*; D006056:Golgi Apparatus / Q000201:enzymology* / Q000276:immunology; D057809:HEK293 Cells; D006367:HeLa Cells; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development / Q000276:immunology; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009024:Morphogenesis; D009154:Mutation; D055495:Neurogenesis; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014162:Transfection; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D018960:Hyaluronan Receptors; D018698:Glutamic Acid; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D019061:src-Family Kinases
keywords: CD44; Dendritic arborization; Extracellular matrix; Golgi fragmentation; Src kinase