Knockdown of INPP5K compromises the differentiation of N2A cells

Annamaria Manzolillo; Lennart Gresing; Christian A Hübner; Patricia Franzka

doi:10.3389/fnmol.2024.1356343

Knockdown of INPP5K compromises the differentiation of N2A cells

Front Mol Neurosci. 2024 Mar 15:17:1356343. doi: 10.3389/fnmol.2024.1356343. eCollection 2024.

Authors

Annamaria Manzolillo¹, Lennart Gresing¹, Christian A Hübner^{1

2}, Patricia Franzka¹

Affiliations

¹ Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
² Center of Rare Diseases, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.

Abstract

Inositol polyphosphate 5-phosphatase K (INPP5K), also known as SKIP (skeletal muscle and kidney-enriched inositol phosphatase), is a cytoplasmic enzyme with 5-phosphatase activity toward phosphoinositides (PIs). Mutations in INPP5K are associated with autosomal recessive congenital muscular dystrophy with cataracts and intellectual disability (MDCCAID). Notably, muscular dystrophy is characterized by the hypoglycosylation of dystroglycan. Thus, far, the underlying mechanisms are only partially understood. In this study, we show that INPP5K expression increases during brain development. Knockdown of INPP5K in the neuroblastoma-derived cell line N2A impaired their neuronal-like differentiation and interfered with protein glycosylation.

Keywords: INPP5K; brain; development; endoplasmic reticulum; glycosylation.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the DFG GRK 2155 ProMoAge to CH. This study was supported by a Medical Scientist Award from the Interdisciplinary Center for Clinical Research (IZKF) at the Jena University Hospital (MSP13) and by IMPULSE funding (FKZ IP 2021-04) from the Friedrich-Schiller-University Jena to PF.