{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302106/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302106"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Loss of Gak leads to lysosome dysfunction and immune modulation in podocytes","description":"Lysosome impairment causes cellular and organ dysfunction, highlighting its crucial role in homeostasis. In this study, we uncovered the indispensable role of cyclin G-associated kinase (GAK) in maintaining podocyte lysosome integrity. We previously showed that podocyte-specific loss of Gak (Gak-KO) leads to severe proteinuria, podocyte injury, and kidney failure. To identify which GAK domains are necessary for its function, we used a transgenic mouse expressing a truncated 62-kDa C-terminal GAK protein (GAK C62). Our findings showed significant accumulation of autophagic vesicles in Gak-KO podocytes, attributed to impaired lysosomal degradation secondary to lysosomal hydrolase mistrafficking. Notably, GAK C62 expression completely rescued these phenotypes at both cellular and organismal levels. Moreover, in vivo RNA-seq and cytokine profiling demonstrated enrichment of immune-related pathways and IL-11 production in Gak-KO podocytes. Overall, this study underscores the importance of lysosome integrity and suggests how its dysfunction may lead podocytes to adopt immune-like properties, with potential autocrine and paracrine effects within the kidney.","dates":{"publication":"2026/06/18"},"accession":"GSE302106","cross_references":{"GSM":["GSM9096291","GSM9096290","GSM9096293","GSM9096292","GSM9096295","GSM9096294","GSM9096297","GSM9096296","GSM9096288","GSM9096299","GSM9096298","GSM9096289"],"GPL":["24247"],"GSE":["302106"],"taxon":["Mus musculus"]}}