Journal
BIOMOLECULES
Volume 10, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/biom10060843
Keywords
S100 proteins; p53; ATAD3A; AHNAK; RPTP sigma; enlargosome; exocytosis; annexin2
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Funding
- Lola Raut and Elisabeth Jorge Foundation
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In mammals, adipose tissue is an active secretory tissue that responds to mild hypothermia and as such is a genuine model to study molecular and cellular adaptive responses to cold-stress. A recent study identified a mammal-specific protein of the endoplasmic reticulum that is strongly induced in the inguinal subcutaneous white adipocyte upon exposure to cold, calsyntenin 3 beta (CLSTN3 beta). CLSTN3 beta regulates sympathetic innervation of thermogenic adipocytes and contributes to adaptive non-shivering thermogenesis. The calcium- and zinc-binding S100B is a downstream effector in the CLSTN3 beta pathways. We review, here, the literature on the transcriptional regulation of the S100b gene in adipocyte cells. We also rationalize the interactions of the S100B protein with its recognized or hypothesized intracellular (p53, ATAD3A, CYP2E1, AHNAK) and extracellular (Receptor for Advanced Glycation End products (RAGE), RPTP sigma) target proteins in the context of adipocyte differentiation and adaptive thermogenesis. We highlight a chaperon-associated function for the intracellular S100B and point to functional synergies between the different intracellular S100B target proteins. A model of non-classical S100B secretion involving AHNAK/S100A10/annexin2-dependent exocytosis by the mean of exosomes is also proposed. Implications for related areas of research are noted and suggestions for future research are offered.
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