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. Author manuscript; available in PMC: 2016 Jul 27.
Published in final edited form as: Dev Cell. 2015 Jul 9;34(2):152–167. doi: 10.1016/j.devcel.2015.06.011

Figure 7. Model of how MBP regulates OL actin disassembly.

Figure 7

(A–C) MBP competes with actin disassembly proteins for binding to PI(4,5)P2. (A and B) 10μM (A) or 1μM (B) recombinant human cofilin-1 protein was incubated with control or PI(4,5)P2 beads with the indicated concentration of native MBP, washed, and bound protein eluted with sample buffer. Immunoblots show bound cofilin (top) and bound MBP (bottom). (C) Densitometry quantification of PI(4,5)P2-bound cofilin as a function of the molar ratio of MBP:cofilin. Inset, bound MBP. n = 3 experimental days. See also Figure S7.

(D–F) Dual RNAi of gelsolin and cofilin phenocopies MBP RNAi. OPCs were transfected with nontargeting siRNA (control, top) or siRNAs targeting gelsolin and cofilin (Gsn+Cfl1, bottom) or MBP (see Figure 6E) then differentiated for 6 days into mature OLs. (D) MBP (red) and actin filaments (phalloidin, green and false colored on right). (E and F) Quantification of width (E) and phalloidin intensity (F) in actin rims at the OL cell edge. *p < 0.05, ***p < 0.001, ***p < 0.0001; Dunnett’s multiple comparisons test; n = 3 experimental days. Error bars: SEM.

(G) Model of how MBP may regulate actin disassembly during myelination. Left, actin disassembly factors cofilin and gelsolin are normally sequestered by PI(4,5)P2 (PIP2), preventing them from disassembling actin filaments. Right, MBP binds to PI(4,5)P2 on the OL membrane, releasing cofilin/gelsolin to disassemble actin.

(H) Two-step model of myelin wrapping. (1) Ensheathment of axons by OL processes requires actin filaments (green), which also limit aberrant myelin membrane growth. (2) Local actin disassembly in the inner tongue induces myelin wrapping.