Laptm4a-KO Mouse

Laptm4a, short for lysosomal-associated protein transmembrane 4A, is a protein-coding gene. It is involved in multiple cellular processes such as lysosomal function regulation and protein-protein interactions. It has been implicated in pathways related to glycolipid biosynthesis, endocytosis, and protein degradation, which are crucial for maintaining normal cellular homeostasis [2,3,4,5].

In glioma, Laptm4a is up-regulated and associated with poor prognosis. It may influence metastasis through the epithelial-mesenchymal transition (EMT) pathway. High Laptm4a-expressing glioma patients are sensitive to doxorubicin [1]. In HeLa cells, disruption of Laptm4a reduces globotriaosylceramide (Gb3) biosynthesis, affecting the post-transcriptional regulation of Gb3 synthase activity [3]. In HEK293 cells, overexpression of Laptm4a negatively regulates the function of human organic cation transporter 2 (hOCT2) by influencing its trafficking to/from the cell membrane [2].

In summary, Laptm4a plays important roles in glycolipid regulation, protein-protein interactions, and cell-membrane trafficking. Its dysregulation is associated with glioma, highlighting its potential as a biomarker and therapeutic target for this disease. The functional studies on Laptm4a using in vitro models have provided insights into its role in specific biological processes relevant to disease conditions [1,2,3].

References:

1. Ding, Yongqi, Jiang, Yike, Zeng, Hong, Xiong, Chengfeng, Huang, Da. 2024. Identification of a robust biomarker LAPTM4A for glioma based on comprehensive computational biology and experimental verification. In Aging, 16, 6954-6989. doi:10.18632/aging.205736. https://pubmed.ncbi.nlm.nih.gov/38613802/

2. Grabner, A, Brast, S, Sucic, S, Schlatter, E, Ciarimboli, G. 2011. LAPTM4A interacts with hOCT2 and regulates its endocytotic recruitment. In Cellular and molecular life sciences : CMLS, 68, 4079-90. doi:10.1007/s00018-011-0694-6. https://pubmed.ncbi.nlm.nih.gov/21553234/

3. Yamaji, Toshiyuki, Sekizuka, Tsuyoshi, Tachida, Yuriko, Kuroda, Makoto, Hanada, Kentaro. 2019. A CRISPR Screen Identifies LAPTM4A and TM9SF Proteins as Glycolipid-Regulating Factors. In iScience, 11, 409-424. doi:10.1016/j.isci.2018.12.039. https://pubmed.ncbi.nlm.nih.gov/30660999/

4. Zhang, Weichao, Yang, Xi, Chen, Liang, Wang, Yanzhuang, Li, Ming. 2021. A  conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation. In PLoS biology, 19, e3001361. doi:10.1371/journal.pbio.3001361. https://pubmed.ncbi.nlm.nih.gov/34297722/

5. Tian, Songhai, Muneeruddin, Khaja, Choi, Mei Yuk, Adam, Rosalyn M, Dong, Min. 2018. Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation. In PLoS biology, 16, e2006951. doi:10.1371/journal.pbio.2006951. https://pubmed.ncbi.nlm.nih.gov/30481169/