Process elongation of oligodendrocytes is promoted by the Kelch-related actin-binding protein Mayven.
Rearrangement of the cytoskeleton leading to the extension of cellular processes is essential for the myelination of axons by oligodendrocytes. We observed that the actin-binding protein, Mayven, is expressed during all stages of the oligodendrocyte lineage, and that its expression is up-regulated during oligodendrocyte differentiation. Mayven is localized in the cytoplasm and along the cell processes. Mayven also binds actin, and is involved in the cytoskeletal reorganization in oligodendrocyte precursor cells (O-2A cells) that leads to process elongation. Mayven overexpression resulted in an increase in the process outgrowth of O-2A cells and in the lengths of the processes, while microinjection of Mayven-specific antibodies inhibited process extension in these cells. Furthermore, O-2A cells transduced with recombinant retroviral sense Mayven (pMIG-W-Mayven) showed an increase in the number of oligodendrocyte processes with outgrowth, while recombinant retroviral antisense Mayven (pMIG-W-Mayven-AS) blocked O-2A process extension. Interestingly, co-localization and association of Mayven with Fyn kinase were found in O-2A cells, and these interactions were increased during the outgrowth of oligodendrocyte processes. This association was mediated via the SH3 domain ligand (a.a. 1-45) of Mayven and the SH3 domain of Fyn, suggesting that Mayven may act as a linker to bind Fyn, via its N-terminus. Thus, Mayven plays a role in the dynamics of cytoskeletal rearrangement leading to the process extension of oligodendrocytes.
Jiang
Shuxian
S
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachussetts 02115, USA.
Avraham
Hava Karsenty
HK
Park
Shin-Young
SY
Kim
Tae-Aug
TA
Bu
Xia
X
Seng
Seyha
S
Avraham
Shalom
S
D000199:Actins / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites / Q000502:physiology; D015152:Blotting, Northern / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D022081:Cell Surface Extensions / Q000187:drug effects* / Q000502:physiology / Q000821:virology; D002478:Cells, Cultured; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D008840:Microfilament Proteins / Q000276:immunology / Q000494:pharmacology*; D008845:Microinjections / Q000379:methods; D018613:Microscopy, Confocal / Q000379:methods; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000494:pharmacology*; D019081:O Antigens / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D016548:Prosencephalon / Q000166:cytology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection / Q000379:methods; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D000906:Antibodies; C485646:KLHL2 protein, human; D008840:Microfilament Proteins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D019081:O Antigens; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; C494957:FYN protein, human; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases