Department of Cell Biology and Neuroscience
College of Medicine
University of South Alabama
Medical Sciences Building 1201
307 University Blvd
Mobile, AL 36688
Tel: (251) 460 6769
Fax: (251) 460 6771
B.Sc.: Shanghai JiaoTong University (1991)
M.Sc.: Shanghai Brain Research Institute (1994)
Ph.D.: University of Iowa (2000)
Postdoc: University of Iowa, with Drs. Steven Green & Michale Dailey
University of Iowa and HHMI, with Dr. Michael J. Welsh
Proton and Neuron Function. Protons are one of the most universal signaling molecules in the brain. While brain pH is tightly regulated, it can fluctuate under physiological and pathological conditions. In particular, various disease conditions, including seizure, stroke, mitochondrial dysfunction and neurodegenerative diseases, all lead to a decrease in extracellular pH, or acidosis. Understanding how proton regulates neuron function thus has important clinical implications. We use a combination of cellular, molecular, biochemical and imaging approaches in our studies, and use both organotypic hippocampal slices and cultured neurons as our model systems. Currently, the lab focuses on two areas:
First, we are studying how acidosis regulates neuron function, including neuronal survival and synaptic remodeling. We are particularly interested in asking how acidosis regulates dendritic spines, because little is known about how a decrease in extracellular pH regulates synaptic plasticity. Our recent results revealed that significant spine remodeling occurs within one hour of acidosis (Jing et al. 2012 J Neurosci). Our current emphasis is on how this phenomenon contributes to changes in diseases like recurrent seizures or ischemia.
Second, we are studying the trafficking mechanisms of acid-sensing ion channels (ASICs). Current studies have shown clearly that ASICs play critical roles in multiple diseases that generate acidosis. However, little is known about the biology underlying ASIC biogenesis and trafficking. Our recent studies showed that N-glycosylation is important for efficient surface expression, dendritic targeting and channel properties of ASIC1a (Jing et al. 2011; Jing et al. 2012). Based on these results, we are currently investigating how a change in ASIC trafficking affects neuronal death in diseases and/or acidosis-induced spine remodeling. We are also asking how different motifs regulate ASIC biogenesis and trafficking. We expect that results from these studies will help us to better understand the role of protons in diseases.
Funding: American Heart Association.
Selected Recent Publications
- Zha XM. (2013) Acid-sensing ion channels: trafficking and synaptic function. Mol Brain 6:1. Free Access
- Jing L*, Chu XP*, Jiang YQ*, Collier DM, Wang B, Jiang Q, Snyder PM and Zha XM. (2012) N-Glycosylation of Acid-sensing Ion Channel 1a Regulates its Trafficking and Acidosis-induced Spine Remodeling. J Neurosci. 32: 4080-91. Free Access
- Jing L, Jiang YQ, Jiang Q, Wang B, Chu XP, and Zha XM. (2011) Interaction between the first transmembrane domain and the thumb of acid-sensing ion channel 1a is critical for its N-glycosylation and trafficking. PLoS One 6: e26909. Free Access
- Lu Y, Zha XM, Kim EY, Schachtele S, Dailey ME, Hall DD, Strack S, Green SH, Hoffman DA, and Hell JW. (2011) A Kinase Anchor Protein150-Associated Protein Kinase A Limits Dendritic Spine Density. J Biol Chem. 286:26496-506. PMCID: PMC3143614.
- Zha XM, Costa V, Harding A, Reznikov L, Price MP, Benson CJ, and Welsh MJ. (2009) ASIC2 Subunits Target Acid-Sensing Ion Channels to the Synapse via an Association with PSD-95. J Neurosci. 29: 8839-46. Free Access
- Zha XM, Dailey ME, and Green SH. (2009) Role of Ca2+/calmodulin-dependent protein kinase II in dendritic spine remodeling during epileptiform activity in vitro. J Neurosci.Res. 87:1969-1979 Free Access
- Zha XM, Wang R, Collier DM, Wemmie JA, Snyder P, and Welsh MJ. (2009) Oxidant Regulated Intersubunit Disulfide Bond Formation between ASIC1a Subunits. Proc. Natl. Acad. Sci. 106: 3573-3578. Free Access
- Zha XM, Wemmie JA, Green SH, and Welsh MJ. (2006) ASIC1a Is a Postsynaptic Proton Receptor that Affects the Density of Dendritic Spines. Proc. Natl. Acad. Sci. 103: 16556-16561. Free Access
- Zha XM, Green SH, and Dailey ME. (2005) Regulation of hippocampal synapse remodeling by epileptiform activity. Mol. Cell. Neurosci. 29(4): 494-506. (*Journal cover)