Map7d2-KO Mouse

Map7d2, a member of the MAP7 family, is a microtubule-associated protein. It plays a crucial role in modulating microtubule (MT) dynamics, which are essential for various cellular processes such as cell motility, neurite outgrowth, and intracellular cargo transport. It is involved in pathways related to the regulation of MT-based functions and may have broader implications for normal cellular development and function [2,3].

In colorectal cancer (CRC) patients with microsatellite stable (MSS) tumors, Map7d2 has been shown to reduce CD8+ cytotoxic T lymphocyte (CTL) infiltration. Knockdown of Map7d2 in in vitro and in vivo experiments significantly increased the infiltration of CD8+ CTLs, inhibiting tumor progression and improving the efficacy of immune checkpoint inhibitors in MSS CRC murine models. Mechanistically, Map7d2 interacts with MYH9, protecting it from ubiquitin-mediated degradation, which in turn decreases the secretion of HMGB1 that suppresses CD8+ CTL infiltration [1]. In neuronal cells, loss of Map7d2 led to decreased resistance to the MT-destabilizing agent nocodazole and increased random cell migration and neurite outgrowth, suggesting its role in MT stabilization [2]. Depletion of Map7d2 in neurons resulted in reduced axonal cargo entry and defects in axon development and neuronal migration, indicating its function in promoting kinesin-1-mediated cargo transport into the axon [3].

In summary, Map7d2 is vital for microtubule-related functions in normal cell processes. Its role in cancer, especially in regulating immune cell infiltration in colorectal cancer, is significant. Studies using gene knockdown (functionally similar to gene knockout in revealing gene function) in in vitro and in vivo models have provided insights into its functions, highlighting its potential as a therapeutic target in CRC and its importance in understanding neuronal development and function.

References:

1. Wu, Qian, Yue, Xiao, Liu, Huashan, Lan, Ping, Wu, Xianrui. 2022. MAP7D2 reduces CD8+ cytotoxic T lymphocyte infiltration through MYH9-HMGB1 axis in colorectal cancer. In Molecular therapy : the journal of the American Society of Gene Therapy, 31, 90-104. doi:10.1016/j.ymthe.2022.09.001. https://pubmed.ncbi.nlm.nih.gov/36081350/

2. Kikuchi, Koji, Sakamoto, Yasuhisa, Uezu, Akiyoshi, Hisanaga, Shin-Ichi, Nakanishi, Hiroyuki. 2022. Map7D2 and Map7D1 facilitate microtubule stabilization through distinct mechanisms in neuronal cells. In Life science alliance, 5, . doi:10.26508/lsa.202201390. https://pubmed.ncbi.nlm.nih.gov/35470240/

3. Pan, Xingxiu, Cao, Yujie, Stucchi, Riccardo, Harterink, Martin, Hoogenraad, Casper C. . MAP7D2 Localizes to the Proximal Axon and Locally Promotes Kinesin-1-Mediated Cargo Transport into the Axon. In Cell reports, 26, 1988-1999.e6. doi:10.1016/j.celrep.2019.01.084. https://pubmed.ncbi.nlm.nih.gov/30784582/