TY - JOUR T1 - Map7D2 and Map7D1 facilitate microtubule stabilization through distinct mechanisms in neuronal cells JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201390 VL - 5 IS - 8 SP - e202201390 AU - Koji Kikuchi AU - Yasuhisa Sakamoto AU - Akiyoshi Uezu AU - Hideyuki Yamamoto AU - Kei-ichiro Ishiguro AU - Kenji Shimamura AU - Taro Saito AU - Shin-ichi Hisanaga AU - Hiroyuki Nakanishi Y1 - 2022/08/01 UR - https://www.life-science-alliance.org/content/5/8/e202201390.abstract N2 - Microtubule (MT) dynamics are modulated through the coordinated action of various MT-associated proteins (MAPs). However, the regulatory mechanisms underlying MT dynamics remain unclear. We show that the MAP7 family protein Map7D2 stabilizes MTs to control cell motility and neurite outgrowth. Map7D2 directly bound to MTs through its N-terminal half and stabilized MTs in vitro. Map7D2 localized prominently to the centrosome and partially on MTs in mouse N1-E115 neuronal cells, which expresses two of the four MAP7 family members, Map7D2 and Map7D1. Map7D2 loss decreased the resistance to the MT-destabilizing agent nocodazole without affecting acetylated/detyrosinated stable MTs, 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. Map7D1 exhibited similar subcellular localization and gene knockdown phenotypes to Map7D2. However, in contrast to Map7D2, Map7D1 was required for the maintenance of acetylated stable MTs. Taken together, our data suggest that Map7D2 and Map7D1 facilitate MT stabilization through distinct mechanisms in cell motility and neurite outgrowth. ER -