• PMID: 29386567
• Gene Name: MGAT1
• Condition: Spermatogenetic defects, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Spermatogenetic defects, Male infertility

MGAT1 and Complex N-Glycans Regulate ERK Signaling During Spermatogenesis

Biswas B, Batista F, Sundaram S, Stanley P.

Mechanisms that regulate spermatogenesis in mice are important to define as they often apply to fertility in man. We previously showed that conditional deletion of the mouse Mgat1 gene (Mgat1 cKO) in spermatogonia causes a germ-cell autonomous defect leading to infertility. MGAT1 is the N-acetylglucosaminyltransferase (GlcNAcT-I) that initiates the synthesis of complex N-glycans. Mechanistic bases of MGAT1 loss were investigated in germ cells from 22- and 23-day males, before any changes in germ cell morphology were apparent. Gene expression changes induced by deletion of Mgat1 were determined using the Affymetrix gene chip Mouse Mogene 2.0 ST array, and relationships were investigated by bioinformatics including Gene Ontology (GO), Ingenuity Pathway Analysis (IPA), and Gene Set Enrichment Analysis (GSEA). The loss of complex N-glycans promoted the premature up-regulation of genes normally expressed later in spermatogenesis and spermiogenesis, and IPA and GSEA implicated ERK signaling. EGFR and PDGFRA transcripts and ERK1/2 signaling were reduced in 22-day Mgat1 cKO germ cells. Basigin, a germ cell target of MGAT1, activated ERK1/2 in CHO cells, but not in a Lec1 CHO mutant that lacks MGAT1 and complex N-glycans. Thus, MGAT1 is required to regulate ERK1/2 signaling during spermatogenesis, potentially via different mechanisms. FAU - Biswas, Barnali AU - Biswas B AD - Department of Cell Biology, Albert Einstein College of Medicine, New York, NY, 10461, USA. FAU - Batista, Frank AU - Batista F AD - Department of Cell Biology, Albert Einstein College of Medicine, New York, NY, 10461, USA. AD - Biochemistry and Molecular Biology Department, University of Debrecen, Debrecen, Hungary. FAU - Sundaram, Subha AU - Sundaram S AD - Department of Cell Biology, Albert Einstein College of Medicine, New York, NY, 10461, USA.