title: Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.
abstract: The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.
authors.affiliation: Nofima AS, Pb 210, NO-1431 Ås, Norway.
authors.forename: Sissel B
authors.initials: SB
authors.lastname: Rønning
authors.affiliation: Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway; KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Cathrine R
authors.initials: CR
authors.lastname: Carlson
authors.affiliation: Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo, Norway.
authors.forename: Espen
authors.initials: E
authors.lastname: Stang
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Svein O
authors.initials: SO
authors.lastname: Kolset
authors.affiliation: Nofima AS, Pb 210, NO-1431 Ås, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Hollung
authors.affiliation: Nofima AS, Pb 210, NO-1431 Ås, Norway.
authors.forename: Mona E
authors.initials: ME
authors.lastname: Pedersen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D008969:Molecular Sequence Data; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D053671:Syndecan-4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D053671:Syndecan-4