Research Interests
Synaptotagmins and the release of pitutiary hormones
The precise control of peptide hormone secretion from the pituitary is essential for regulating vertebrate physiology and homeostasis, as these hormones control diverse processes including growth, metabolism, and reproduction. The anterior pituitary consists of five major cell types which secrete specific hormones. Gonadotropes are the only pituitary cell type that secrete two hormones: follicle stimulating hormone (FSH) and lutenizing hormone (LH); however, they are differentially released, and this difference is necessary for their physiological action. Tropic hormones released by the hypothalamus trigger Ca2+ oscillations in anterior pituitary cells with specific patterns (amplitudes and frequencies) that can differentially trigger the release of each hormone. The signaling steps through which tropic hormone-receptor interactions mobilize intracellular Ca2+ are well understood; however, little is known concerning the Ca2+ sensors that ‘decode’ these oscillations to trigger exocytosis.
The synaptotagmin (syt) family of proteins have been shown to play crucial roles in the regulation of exocytosis in neurons and neuroendocrine cells. Seventeen isoforms of syt have been identified in mammals, and many, but not all bind to - and are activated by - Ca2+. Moreover, the affinity of syts for Ca2+ can differ greatly between distinct isoforms, indicating that syts might be able to differentially integrate Ca2+ signals in cells.
The emerging view is that many, if not most, isoforms of syt are large dense core vesicle (LDCV) proteins. The pituitary harbors the greatest variety of LDCVs, but little is known concerning the expression and function of syts in this gland. By elucidating the role of the syt family in the pituitary we could answer multiple questions concerning syt function as well as specific molecular mechanisms responsible for hormone release. Additionally, an unresolved issue with syts in neurons and neuroendocrine cells is whether different syt isoforms expressed in the same cell sort to distinct vesicles, or whether multiple syt isoforms can be localized to the same vesicle. This is critical to our understanding of how LDCVs decode and integrate Ca2+ signals. A better understanding of the molecular machinery responsible for the highly controlled release of pituitary hormones could elucidate mechanisms of disease and provide new pharmaceutical targets.
The precise control of peptide hormone secretion from the pituitary is essential for regulating vertebrate physiology and homeostasis, as these hormones control diverse processes including growth, metabolism, and reproduction. The anterior pituitary consists of five major cell types which secrete specific hormones. Gonadotropes are the only pituitary cell type that secrete two hormones: follicle stimulating hormone (FSH) and lutenizing hormone (LH); however, they are differentially released, and this difference is necessary for their physiological action. Tropic hormones released by the hypothalamus trigger Ca2+ oscillations in anterior pituitary cells with specific patterns (amplitudes and frequencies) that can differentially trigger the release of each hormone. The signaling steps through which tropic hormone-receptor interactions mobilize intracellular Ca2+ are well understood; however, little is known concerning the Ca2+ sensors that ‘decode’ these oscillations to trigger exocytosis.
The synaptotagmin (syt) family of proteins have been shown to play crucial roles in the regulation of exocytosis in neurons and neuroendocrine cells. Seventeen isoforms of syt have been identified in mammals, and many, but not all bind to - and are activated by - Ca2+. Moreover, the affinity of syts for Ca2+ can differ greatly between distinct isoforms, indicating that syts might be able to differentially integrate Ca2+ signals in cells.
The emerging view is that many, if not most, isoforms of syt are large dense core vesicle (LDCV) proteins. The pituitary harbors the greatest variety of LDCVs, but little is known concerning the expression and function of syts in this gland. By elucidating the role of the syt family in the pituitary we could answer multiple questions concerning syt function as well as specific molecular mechanisms responsible for hormone release. Additionally, an unresolved issue with syts in neurons and neuroendocrine cells is whether different syt isoforms expressed in the same cell sort to distinct vesicles, or whether multiple syt isoforms can be localized to the same vesicle. This is critical to our understanding of how LDCVs decode and integrate Ca2+ signals. A better understanding of the molecular machinery responsible for the highly controlled release of pituitary hormones could elucidate mechanisms of disease and provide new pharmaceutical targets.