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Int J Biol Sci 2013; 9(9):948-959. doi:10.7150/ijbs.6426

Review

Glutamate, Glutamate Receptors, and Downstream Signaling Pathways

Stacey S. Willard, Shahriar Koochekpour

Departments of Cancer Genetics and Urology, Center for Genetics and Pharmacology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, USA.

Abstract

Glutamate is a nonessential amino acid, a major bioenergetic substrate for proliferating normal and neoplastic cells, and an excitatory neurotransmitter that is actively involved in biosynthetic, bioenergetic, metabolic, and oncogenic signaling pathways. Glutamate signaling activates a family of receptors consisting of metabotropic glutamate receptors (mGluRs) and ionotropic glutamate receptors (iGluRs), both of which have been implicated in chronic disabling brain disorders such as Schizophrenia and neurodegenerative diseases like Alzheimer's, Parkinson's, and multiple sclerosis. In this review, we discuss the structural and functional relationship of mGluRs and iGluRs and their downstream signaling pathways. The three groups of mGluRs, the associated second messenger systems, and subsequent activation of PI3K/Akt, MAPK, NFkB, PLC, and Ca/CaM signaling systems will be discussed in detail. The current state of human mGluR1a as one of the most important isoforms of Group I-mGluRs will be highlighted. The lack of studies on the human orthologues of mGluRs family will be outlined. We conclude that upon further study, human glutamate-initiated signaling pathways may provide novel therapeutic opportunities for a variety of non-malignant and malignant human diseases.

Keywords: Glutamate, mGluR, iGluR, GRM1a, signaling.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Willard SS, Koochekpour S. Glutamate, Glutamate Receptors, and Downstream Signaling Pathways. Int J Biol Sci 2013; 9(9):948-959. doi:10.7150/ijbs.6426. Available from http://www.ijbs.com/v09p0948.htm