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Description

Calsyntenin 3beta (UniProt: A0A4P8DYG6, also known as Calsyntenin-3beta, CLSTN3beta) is encoded by the Clstn3 (also known as Clstn3b) gene (Gene ID: 232270) in murine species. CLSTN3beta is a mammal-specific that is preferentially expressed in thermogenic adipocytes and is localized in endoplasmic reticulum. Its expression in brown adipose tissue is about six-fold higher than both the inguinal subcutaneous and the perigonadal visceral white adipose tissue. However, its expression can be induced in the inguinal subcutaneous white adipose tissue upon cold exposure. Brown adipose tissue thermogenesis require innervation by the sympathetic nerves that release norepinephrine, which activates beta-adrenergic receptors-cAMP-PKA pathway to drive lipolysis and thermogenic respiration. CLSTN3beta is shown to promote S100b protein release that promotes this innervation and its loss is shown to reduce functional sympathetic innervation in adipose tissue. Loss of CLSTN3beta also predisposes mice to obesity on a high fat diet. Clstn3beta knockout mice exhibit significantly higher fasting glucose levels, impaired glucose tolerance, more lipid accumulation in brown adipose tissue, and liver steatosis. (Ref.: Pluci?ska, K., et al. (2020). Front. Endocrinol. 11, 579785, Zeng, X., et al. (2019). Nature. 569(7755), 229-235).