Gregory W. Aponte
Our laboratory has been focused on identifying and characterizing mechanisms by which dietary nutrients act as signaling molecules (before they are metabolized), causing changes in gene regulation and/or secretory responses of intestinal and peripheral tissues and nerves. We discovered that the G protein coupled receptor (GPCR) LPA5 can be activated by proteins in lymphatic fluid derived from the diet. We further established that sensory neurons expressing GPCRs, similar to LPA5, can respond to molecules in the lymphatic fluid from the intestine and peripheral tissue through a “neurolymphocrine system”. Our laboratory is characterizing this new pathway whereby dietary molecules, and other signal molecules from peripheral tissues, can activate local neurons that signal the central nervous system (CNS). We are determining the signaling pathways that occurs when a biologically active molecule enters the lymphatic system and acts as a "Iymphocrine", analogous to a hormone or neuroendocrine molecule. The characterization of the neurolymphocrine system: 1) Expands the concept of gut-brain axis by providing a mechanism whereby dietary induced changes in the lumen or mucosal secretions can directly activate CNS sensory nerves. 2) Establishes that the lymphatic system is a vehicle that transports biologically active molecules that act locally (as paracrines) and enables them to act at distant targets through sensory nerves. 3) Provides a new mechanism for regulation of enteric neuroactive peptide synthesis and secretion. 4) Provides a new pathway for the regulation of CNS activity and behavior in response to peripheral molecules by providing a means to act as signal molecules rather than just substrates for metabolism.
Aponte GW, Park K, Hess R, Garcia R, and Taylor IL. 1989. Meal-induced peptide tyrosine tyrosine inhibition of pancreatic secretion in the rat. FASEB J 3: 1949-1955.
Lee M, Hadi M, Halldén G, and Aponte GW. 2005. Peptide YY and neuropeptide Y induce expression, reduce adhesion, and enhance migration in small intestinal cells through the regulation of CD63, matrix metalloproteinase-3, and Cdc42 activity. J Biol Chem 280: 125-36.
Choi S, Lee M, Shiu AL, Yo SJ, and Aponte GW. 2007. Identification of a protein hydrolysate responsive G protein coupled receptor in enterocytes. Am J Physiol Gastrointest Liver Physiol 292: G98-G112.
Choi S, Lee M, Yo SJ, Shiu AL, Halldén G, and Aponte GW. 2007. GPR93 activation by protein hydrolysate induces CCK transcription and secretion in STC-1 cells. Am J Physiol Gastrointest Liver Physiol 292: G1366-1375.
Poole DP1, Lee M, Tso P, Bunnett NW, Yo SJ, Lieu T, Shiu A, Wang JC, Nomura DK, Aponte GW (2014) Am J Physiol Gastrointest Liver Physiol. 2014 Apr 15;306(8):G686-98 Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system.
A key discovery finds nutrient molecules that send message to the brain. Article featured in BREAKTHROUGHS magazine.