Mechanisms controlling the expression of the components of the exocytotic apparatus under physiological and pathological conditions

Abstract

The last decade has witnessed spectacular progress in the identification of the protein apparatus required for exocytosis of neurotransmitters, peptide hormones and other bioactive products. In striking contrast, our knowledge of the mechanisms determining the expression of the components of the secretory machinery has remained rudimentary. Since modifications in secretory functions are associated with several physiological processes and contribute to the development of human pathologies, a better knowledge of the control of the expression of the genes involved in exocytosis is urgently needed. Recent studies have led to the identification of transcription factors and other regulatory molecules such as microRNAs that modulate the cellular level of key controllers of the exocytotic process. These findings furnish a new perspective for understanding how secretory functions can adapt to normal physiological conditions and shed light on the mechanisms involved in the development of important human diseases such as diabetes mellitus characterized by defective release of bioactive compounds.

Identification of microRNAs with a role in glucose stimulated insulin secretion by expression profiling of MIN6 cells

“…Mir-124a affects the expression of a number of other exocytosis related proteins in MIN6 B1 cells including SNAP25, Rab3A, synapsin-1A, Rab27A and Noc2; although only Rab27A is a direct target of mir-124a [4]. These exocytosisrelated proteins also have predicted binding sites for regulation by other miRNAs, but these still remain to be experimentally validated [22].…”

Connexins: Key Mediators of Endocrine Function

“…The same element is also repressed by high concentrations of palmitate, in vitro and in vivo (4). The effects of both glucose and palmitate are mediated by the cAMP-dependent overexpression of the inducible cAMP early repressor repressor ICER-1, which adversely affects ␤-cell function and proliferation (1,4,6,232,233). If the same effect was to occur in human ␤-cells exposed to long-term hyperglycemia, a logical therapeutic measure would be to restore normal levels of Cx36.…”

Energizing miRNA research: A review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways

“…Myotrophin is evidently the target of miR-375, and this miRNA:target interaction regulates the secretion of insulin. The regulation of exocytosis machinery is probably a widespread phenomenon because many miRNAs are predicted to target exocytosis-related proteins [41]. Plaisance et al [54] showed that miR-9 causes a reduction in exocytosis in pancreas (insulinsecreting beta cells) that is elicited by stimuli including glutamate.…”

“…Accordingly, miRNAs participate in metabolism--making energy available to an organism. Thus far research in this field is in its infancy, and much remains to be learned (for excellent prior reviews, see [41][42][43][44]). Some research findings will be summarized below with an emphasis on the metabolism of lipids.…”