Faculty Mentor

Dr. Elaine Vanterpool

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Description

Polycystic ovary syndrome (PCOS) is a hormonal imbalance disorder unique to females that primarily affects the ovaries. It is common in women of reproductive age and characterized by irregular menstrual cycles and further health issues include diabetes type 2, ovarian cysts and infertility. Many women with PCOS have insulin resistance. CAPN10 is the first diabetes gene to be identified through a genome scan. It was also found to be associated with other Cardiometabolic disease and PCOS. CAPN10 gene also known as the calpain-10 is a calcium dependent cysteine protease. This means its activity is regulated by calcium ions and it functions as an enzyme. It is present on chromosome 2q37.3 and has 12 exons. It encodes a protein that plays a role in insulin sensitivity and glucose homeostasis by regulating actin dynamics within cells. Thus, it has great importance in the beta-cells. CAPN10 has been found to facilitate GLUT4 translocation and acts in reorganization of the cytoskeleton. The latter is necessary for proper insulin granule trafficking and exocytosis. Polymorphism in CAPN10 leads to PCOS because insulin resistance is associated with PCOS. Through its function as a cysteine protease, CAPN10 plays a role in regulating insulin sensitivity. Mutations can cause CAPN10 to not function correctly, leading to decrease in insulin sensitivity and resulting in insulin resistance. A proposed mechanism for Calpain-10 gene activation is when glucose enters the cell, it increases the glucose absorption and metabolism raises ATP levels. This in turn causes inactivation of ATP-sensitive potassium channels, membrane depolarization, and calcium influx and affects insulin secretion. Subdomain Ⅲ and domains Ⅱa and Ⅱb are the conserved domains affected by the four variants of CAPN10, single nucleotide missense mutations, Arg555Cys, Ala156Thr, Ser613Asn, and Pro320Leu. Subdomain Ⅲ and domains Ⅱa and Ⅱb function in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction. As well as calcium- induced activation and electrostatic interactions with subdomain II. Mutations in these areas are likely to have a significant impact on catalytic activity.

Publication Date

4-1-2025

City

Huntsville

Disciplines

Biology

Comments

Gabrielle Murray, Student Researcher

Analysis of the CAPN10 Gene In Women With Polycystic Ovary Syndrome

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Biology Commons

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