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. 2013 Aug 6;4:96. doi: 10.3389/fendo.2013.00096

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Copyright © 2013 Lin and Salton.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Regulated secretory pathway of a model neuroendocrine cell. Single nucleotide polymorphisms (SNPs) can affect granule biogenesis and release through these mechanisms: (1) SNPs in the promoter or 3′UTR of granule-associated genes modulate gene expression levels, resulting in altered granule biogenesis, (2) SNPs in the pro-domain of peptides or hormones block their processing and/or sorting into the regulated pathway, (3) SNPs in convertase/peptidase catalytic or regulatory domains reduce enzymatic activity and lead to aberrant propeptide processing, (4) SNPs in the signal peptide and/or sorting domain(s) disrupt regulated secretion, and (5) SNPs that change the processing or sequence of neuropeptides modulate membrane receptor binding affinity. TrkB, tropomyosin-related kinase B receptor; INSR, insulin receptor.