Kif13a-KO Mouse

Kif13a, a member of the kinesin-3 family, is an ATP-dependent motor protein. It associates with recycling endosomes and regulates their membrane dynamics, playing a crucial role in multiple cellular functions such as cargo transport, recycling endosomal tubule biogenesis, cell polarity, migration, and cytokinesis [1]. It is involved in various cellular pathways related to endocytic recycling and microtubule-based vesicle transport [1,2,3,4,6,7,8,9]. Genetic models, like knockout (KO) mouse models, are valuable for studying its functions.

In neurons, knockout of Kif13a affects the polarized vesicular transport of transferrin receptor-containing vesicles, revealing its role in ensuring proper dendritic-axonal polarization [2,5]. In HeLaM cells, knockout of Rab10, which interacts with Kif13A, abolishes tubular endosomal structures, suggesting Kif13a's role in tubular endosome formation [6]. Depletion of Kif13a in influenza A-infected cells reduces viral titers and vRNP accumulation at the cell surface, highlighting its importance in viral ribonucleoprotein trafficking [7]. In cancer cells, knockdown of Kif13a inhibits MT1-MMP-dependent collagen degradation and invasion, indicating its role in cancer cell invasion [9].

In conclusion, Kif13a is essential for endosomal membrane remodeling and microtubule-based vesicle transport in various biological processes. Model-based research, especially KO/CKO mouse models, has shown its significance in diseases such as influenza A infection and cancer, providing insights into potential therapeutic targets for these conditions.

References:

1. Thankachan, Jerrin Mathew, Setty, Subba Rao Gangi. 2022. KIF13A-A Key Regulator of Recycling Endosome Dynamics. In Frontiers in cell and developmental biology, 10, 877532. doi:10.3389/fcell.2022.877532. https://pubmed.ncbi.nlm.nih.gov/35547822/

2. Han, Yue, Li, Min, Zhao, Bingqing, Xu, Jiaxi, Yang, Rui. 2024. MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2316266121. doi:10.1073/pnas.2316266121. https://pubmed.ncbi.nlm.nih.gov/38709923/

3. Patel, Nishaben M, Siva, Meenakshi Sundaram Aravintha, Kumari, Ruchi, Sivaramakrishnan, Sivaraj, Soppina, Virupakshi. 2021. KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell. In Science advances, 7, . doi:10.1126/sciadv.abd2054. https://pubmed.ncbi.nlm.nih.gov/33536208/

4. Gutiérrez, Yolanda, López-García, Sergio, Lario, Argentina, Delevoye, Cédric, Esteban, José A. 2021. KIF13A drives AMPA receptor synaptic delivery for long-term potentiation via endosomal remodeling. In The Journal of cell biology, 220, . doi:10.1083/jcb.202003183. https://pubmed.ncbi.nlm.nih.gov/33999113/

5. Han, Yue, Li, Min, Zhao, Bingqing, Xu, Jiaxi, Yang, Rui. 2023. MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.07.11.548513. https://pubmed.ncbi.nlm.nih.gov/38105964/

6. Etoh, Kan, Fukuda, Mitsunori. 2019. Rab10 regulates tubular endosome formation through KIF13A and KIF13B motors. In Journal of cell science, 132, . doi:10.1242/jcs.226977. https://pubmed.ncbi.nlm.nih.gov/30700496/

7. Ramos-Nascimento, Ana, Kellen, Bárbara, Ferreira, Filipe, Delevoye, Cédric, Amorim, Maria João. 2017. KIF13A mediates trafficking of influenza A virus ribonucleoproteins. In Journal of cell science, 130, 4038-4050. doi:10.1242/jcs.210807. https://pubmed.ncbi.nlm.nih.gov/29061883/

8. Gong, Xiaowei, Didan, Yuliia, Lock, John G, Strömblad, Staffan. 2018. KIF13A-regulated RhoB plasma membrane localization governs membrane blebbing and blebby amoeboid cell migration. In The EMBO journal, 37, . doi:10.15252/embj.201898994. https://pubmed.ncbi.nlm.nih.gov/30049714/

9. Gifford, Valentina, Woskowicz, Anna, Ito, Noriko, Dustin, Michael L, Itoh, Yoshifumi. 2022. Coordination of two kinesin superfamily motor proteins, KIF3A and KIF13A, is essential for pericellular matrix degradation by membrane-type 1 matrix metalloproteinase (MT1-MMP) in cancer cells. In Matrix biology : journal of the International Society for Matrix Biology, 107, 1-23. doi:10.1016/j.matbio.2022.01.004. https://pubmed.ncbi.nlm.nih.gov/35122963/