Map7D2 and Map7D1 facilitate MT stabilization through distinct mechanisms to control cell motility and neurite outgrowth

Abstract

AbstractMicrotubule (MT) dynamics are modulated through the coordinated action of various MT-associated proteins (MAPs). However, the regulatory mechanisms underlying MT dynamics remain unclear. Herein, we show that MAP7 family protein Map7D2 facilitates MT stabilization to control cell motility and neurite outgrowth. Map7D2, was highly expressed in the brain and testis, directly bound to MTs through its N-terminal half similarly to Map7, and promoted MT stabilization in vitro. Map7D2 localized prominently to the centrosome and partially on MTs in N1-E115 mouse neuroblastoma cells, which expresses two of the four MAP7 family members, Map7D2 and Map7D1. Map7D2 loss decreased the intensity of MTs without affecting stable MT markers acetylated and detyrosinated tubulin, suggesting that Map7D2 stabilizes MTs via direct binding. In addition, Map7D2 loss increased the rate of random cell migration and neurite outgrowth, presumably by disturbing the balance between MT stabilization and destabilization. The other MAP7 family protein expressed in N1-E115, Map7D1, exhibited similar subcellular localization and gene knock-down phenotypes. However, in contrast to Map7D2, Map7D1 was required for the maintenance of acetylated tubulin levels. Taken together, our data suggest that Map7D2 and Map7D1 facilitate MT stabilization through distinct mechanisms for the control of cell motility and neurite outgrowth.