title: CD44 is expressed in non-myelinating Schwann cells of the adult rat, and may play a role in neurodegeneration-induced glial plasticity at the neuromuscular junction.
abstract: CD44 is a multifunctional cell surface glycoprotein which regulates cell-cell and cell-matrix interactions in a variety of tissues. In particular, the protein was found to be expressed in glial cells of developing, but not adult, peripheral nerves, where it takes part in signaling mediated by ErbB class of receptors for neuregulins. Here, we demonstrate, using high resolution morphological methods, tissue fractionation and RT-PCR, that CD44 is strongly expressed in terminal Schwann cell (TSC) at the neuromuscular junction (NMJ) of the adult rat skeletal muscle. As CD44 is also expressed by Schwann cells of the non-myelinated Remak bundles of the proximal peripheral nerves, it appears to be a marker of non-myelinating Schwann cell subpopulation. The analysis of transgenic rats bearing a mutated superoxide-dismutase gene (SOD1(G93A)) causing familial amyotrophic lateral sclerosis (ALS) revealed that TSC activation and morphological plasticity at the NMJ, caused by ongoing denervation-reinnervation is associated with a strong increase in CD44 expression therein. Notably, CD44 immunoreactivity is present in fine axon-escheating processes of the glial cells that guide reinnervation. In addition, we found that both in normal and SOD1(G93A) muscle, CD44 expressed in TSC partially colocalizes with immunoreactivities of neuregulin receptors ErbB2 and ErbB3. The colocalization appears to reflect a physical interaction, as evidenced by co-immunoprecipitation and fluorescence resonance energy transfer (FRET) analysis between CD44 and ErbB3. Importantly, TSC activation upon ALS-like neurodegeneration results in significant increase in molecular proximity of CD44 and ErbB3, which may have an impact on glial plasticity at the NMJ.
authors.affiliation: Nencki Institute of Experimental Biology, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Gorlewicz
authors.forename: Jakub
authors.initials: J
authors.lastname: Wlodarczyk
authors.forename: Ewa
authors.initials: E
authors.lastname: Wilczek
authors.forename: Maciej
authors.initials: M
authors.lastname: Gawlak
authors.forename: Anna
authors.initials: A
authors.lastname: Cabaj
authors.forename: Henryk
authors.initials: H
authors.lastname: Majczynski
authors.forename: Klaudia
authors.initials: K
authors.lastname: Nestorowicz
authors.forename: Magdalena Aneta
authors.initials: MA
authors.lastname: Herbik
authors.forename: Pawel
authors.initials: P
authors.lastname: Grieb
authors.forename: Urszula
authors.initials: U
authors.lastname: Slawinska
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Wilczynski
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D031541:Fluorescence Resonance Energy Transfer; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009410:Nerve Degeneration / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism / Q000648:ultrastructure; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3 / Q000032:analysis / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D006023:Glycoproteins; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C000606292:Sod1 protein, rat; C483804:Erbb2 protein, rat