Myosin Va Controls Oligodendrocyte Morphogenesis and Myelination

Sloane, Jacob A.; Vartanian, Timothy

doi:10.1523/jneurosci.2326-07.2007

Cited by 38 publications

(40 citation statements)

References 54 publications

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“…Possibly, additional redundant pathways controlled by other R-SNAREs such as VAMP2 and VAMP4 account for surface transport in oligodendrocytes. It has been shown that ablation of myosin-Va affects VAMP2 localization and functional inactivation of VAMP2 by application of blocking antibodies or treatment with TeNT (certainly also inactivating VAMP3) affects oligodendroglial process growth (Sloane and Vartanian, 2007).…”

Section: Discussionmentioning

confidence: 99%

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Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7

Feldmann¹,

Amphornrat²,

Schönherr³

et al. 2011

J. Neurosci.

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CNS myelination by oligodendrocytes requires directed transport of myelin membrane components and a timely and spatially controlled membrane expansion. In this study, we show the functional involvement of the R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (R-SNARE) proteins VAMP3/cellubrevin and VAMP7/TI-VAMP in myelin membrane trafficking. VAMP3 and VAMP7 colocalize with the major myelin proteolipid protein (PLP) in recycling endosomes and late endosomes/lysosomes, respectively. Interference with VAMP3 or VAMP7 function using small interfering RNA-mediated silencing and exogenous expression of dominantnegative proteins diminished transport of PLP to the oligodendroglial cell surface. In addition, the association of PLP with myelin-like membranes produced by oligodendrocytes cocultured with cortical neurons was reduced. We furthermore identified Syntaxin-4 and Syntaxin-3 as prime acceptor Q-SNAREs of VAMP3 and VAMP7, respectively. Analysis of VAMP3-deficient mice revealed no myelination defects. Interestingly, AP-3␦-deficient mocha mice, which suffer from impaired secretion of lysosome-related organelles and missorting of VAMP7, exhibit a mild dysmyelination characterized by reduced levels of select myelin proteins, including PLP. We conclude that PLP reaches the cell surface via at least two trafficking pathways with distinct regulations: (1) VAMP3 mediates fusion of recycling endosomederived vesicles with the oligodendroglial plasma membrane in the course of the secretory pathway; (2) VAMP7 controls exocytosis of PLP from late endosomal/lysosomal organelles as part of a transcytosis pathway. Our in vivo data suggest that exocytosis of lysosomerelated organelles controlled by VAMP7 contributes to myelin biogenesis by delivering cargo to the myelin membrane.

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Section: Discussionmentioning

confidence: 99%

“…toward potential myelin defects in patients suffering from diseases characterized by defects in lysosomal secretion such as Griscelli syndrome (Sloane and Vartanian, 2007).…”

Section: Role Of Vamp3 and Vamp7 In Myelinationmentioning

confidence: 99%

Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7

Feldmann¹,

Amphornrat²,

Schönherr³

et al. 2011

J. Neurosci.

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“…During normal development it is associated with an increased expression of myelin proteins, such as myelin basic protein (MBP) (Zeller et al, 1985;Dubois-Dalcq et al, 1986;Hardy and Friedrich, 1996). Under experimental conditions, morphological maturation of oligodendrocytes can occur in the absence of an increase in myelin gene expression, suggesting that these two events may be regulated independently from each other (Buttery and ffrenchConstant, 1999;Osterhout et al, 1999;Sloane and Vartanian, 2007). In the case of PD-Iα/ ATX's MORFO domain we currently favor a model in which primarily morphological remodeling is affected.…”

Section: Discussionmentioning

confidence: 99%

Phosphodiesterase-Iα/autotaxin's MORFO domain regulates oligodendroglial process network formation and focal adhesion organization

Dennis

White

Forrest

et al. 2008

Molecular and Cellular Neuroscience

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Development of a complex process network by maturing oligodendrocytes is a critical but currently poorly characterized step toward myelination. Here, we demonstrate that the matricellular oligodendrocyte-derived protein phosphodiesterase-Iα/autotaxin (PD-Iα/ATX) and especially its MORFO domain are able to promote this developmental step. In particular, the single EF hand-like motif located within PD-Iα/ATX's MORFO domain was found to stimulate the outgrowth of higher order branches but not process elongation. This motif was also observed to be critical for the stimulatory effect of PD-Iα/ATX's MORFO domain on the reorganization of focal adhesions located at the leading edge of oligodendroglial protrusions. Collectively, our data suggest that PD-Iα/ATX promotes oligodendroglial process network formation and expansion via the cooperative action of multiple functional sites located within the MORFO domain and more specifically, a novel signaling pathway mediated by the single EF hand-like motif and regulating the correlated events of process outgrowth and focal adhesion organization.

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“…Ppp1r14a is a phosphorylationdependent inhibitory protein for myosin phosphatase, which regulates myosin activity by dephosphorylation of myosin light chain (Ito et al, 2004). Notably, myosin Va-null mice exhibit significantly impaired myelination in the CNS (Sloane and Vartanian, 2007), raising the possibility that Ppp1r14a regulates oligodendrocyte differentiation. Ppp1r14a can promote tumorigenesis by regulating activity of the Nf2/ Merlin tumor suppressor by means of myosin phosphatase (Jin et al, 2006).…”

Section: Validation Of Oligodendrocyte Gene Identification By In Situmentioning

confidence: 99%

Identification of genes expressed by zebrafish oligodendrocytes using a differential microarray screen

Takada

Appel

2010

Developmental Dynamics

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Myelination of central nervous system axons requires that oligodendrocytes extend multiple membrane processes that specifically recognize and wrap axons, which is followed by expression of proteins necessary for formation of myelin sheaths. To identify new genes that might be important for myelination, we used microarrays to analyze the expression profiles of cells sorted from transgenic zebrafish embryos and larvae under conditions that permitted or blocked oligodendrocyte development. Here, we describe eight genes that have not been previously implicated in oligodendrocyte development. Among the predicted functions of proteins encoded by these genes are lipid sensing, cell-cell junction formation, cytoskeleton regulation, and intracellular signaling. The predicted functions raise the possibility that these genes are involved in multiple cellular events during oligodendrocyte differentiation and myelin formation.

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Myosin Va Controls Oligodendrocyte Morphogenesis and Myelination

Cited by 38 publications

References 54 publications

Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7

Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7

Phosphodiesterase-Iα/autotaxin's MORFO domain regulates oligodendroglial process network formation and focal adhesion organization

Identification of genes expressed by zebrafish oligodendrocytes using a differential microarray screen

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