Process elongation of oligodendrocytes is promoted by the Kelch-related protein MRP2/KLHL1.
Oligodendrocytes (OLGs) are generated by progenitor cells that are committed to differentiating into myelin-forming cells of the central nervous system. Rearrangement of the cytoskeleton leading to the extension of cellular processes is essential for the myelination of axons by OLGs. Here, we have characterized a new member of the Kelch-related protein family termed MRP2 (for Mayven-related protein 2) that is specifically expressed in brain. MRP2/KLHL1 is expressed in oligodendrocyte precursors and mature OLGs, and its expression is up-regulated during OLG differentiation. MRP2/KLHL1 expression was abundant during the specific stages of oligodendrocyte development, as identified by A2B5-, O4-, and O1-specific oligodendrocyte markers. MRP2/KLHL1 was localized in the cytoplasm and along the cell processes. Moreover, a direct endogenous association of MRP2/KLHL1 with actin was observed, which was significantly increased in differentiated OLGs compared with undifferentiated OLGs. Overexpression of MRP2/KLHL1 resulted in a significant increase in the process extension of rat OLGs, whereas MRP2/KLHL1 antisense reduced the process length of primary rat OLGs. Furthermore, murine OLGs isolated from MRP2/KLHL1 transgenic mice showed a significant increase in the process extension of OLGs compared with control wild-type murine OLGs. These studies provide insights into the role of MRP2/KLHL1, through its interaction with actin, in the process elongation of OLGs.
Jiang
Shuxian
S
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
Seng
Seyha
S
Avraham
Hava Karsenty
HK
Fu
Yigong
Y
Avraham
Shalom
S
D018528:ATP-Binding Cassette Transporters; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism* / Q000502:physiology*; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009836:Oligodendroglia / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017386:Sequence Homology, Amino Acid
D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D000199:Actins; C412617:KLHL1 protein, human; C514889:KLHL1 protein, mouse; D008840:Microfilament Proteins