Office: 182 Rightmire Hall
Lab: 138 Rightmire Hall
Lab web page:
Ph.D. - The University of Colorado Health Sciences Center
Post Doctoral - The University of California, San Francisco
My laboratory studies the mechanism and function of neuronal electrical signaling in health and disease.
Action potentials propagating along axons play a central role in rapid cell-to-cell communication over long distances in the nervous system. Action potential initiation and propagation minimally require sequential activation of voltage-gated Na+ (Nav) and K+ (Kv) channels, as discovered by Hodgkin and Huxley in the 1950s. The genes for these channels started to be cloned in the 1980s. Building on those early structure-function studies, our recent studies have contributed to a better understanding of the mechanisms underlying axonal transport and targeting of both Nav and Kv channels in axons.
Our studies identified the axonal targeting motifs and mechanisms governing polarized axon-dendrite targeting of Kv1 and Kv3 channels, the two major Kv channel subfamilies whose members are present and operate in axons. Although these channel proteins are transported by different kinesin molecular motors, both Kv1 and Kv3 require proper channel assembly through the N-terminal T1 domain for axonal transport. This appears to be a conserved quality-control mechanism by which a neuron ensures that only properly assembled and functioning channel proteins are transported into its axons. By contrast, axonal transport of Nav channels is likely mediated by a distinct group of kinesin motors through ankyrin adaptor proteins. Importantly, we showed that axonal membrane targeting of Kv3.1, especially close to the axon initial segment, can further increase the maximal firing frequency of action potentials in neurons. These results may contribute to a better understanding of a novel form of neuronal plasticity via changes of polarized targeting of key membrane proteins.
Currently, we are focusing on understanding ion channel regulation relevant to several brain disorders, including multiple sclerosis, schizophrenia, epilepsy, concussive brain injury, etc.
- Jukkola P, & Gu C* (2015) Regulation of neurovascular coupling in autoimmunity to water and ion channels. Autoimmunity Reviews 14, 258-267; PMCID: PMC4303502
- Gu Y, & Gu C* (2014) Physiological and pathological functions of mechanosensitive ion channels. Molecular Neurobiology 50, 339-347; PMCID: PMC4134430
- Barry J, Gu Y, Jukkola P, O’Neill B, Gu H, Mohler PJ, Thirtamara-Rajamani K, & Gu C* (2014) Ankyrin-G directly binds to kinesin-1 to transport voltage-gated Na+ channels into axons. Developmental Cell 28, 117-131; PMCID: PMC3970081
- Jukkola P, Guerrero T, Gray V, & Gu C* (2013) Astrocytes differentially respond to inflammatory autoimmune insults and imbalances of neural activity. Acta Neuropathologica Communications 1, 70; PMCID: PMC3893391
- Barry J, & Gu C* (2013) Coupling Mechanical Forces to Electrical Signaling: Molecular Motors and the Intracellular Transport of Ion Channels. The Neuroscientist 19, 145-159; PMCID: PMC3625366
- Barry J, Xu M, Gu Y, Dangel A, Shrestha C, & Gu C* (2013) Activation of conventional kinesin motors in clusters by Shaw voltage-gated potassium channels. Journal of Cell Science 126, 2027-2041; PMCID: PMC3666255
- Gu Y, Barry J, & Gu C* (2013) Zinc regulates Kv3 channel assembly, trafficking and activity through different binding sites. Journal of Physiology 591, 2491-2507; PMCID: PMC3678039
- Green JA, Gu C, & Mykytyn K (2012) Heteromerization of ciliary G protein-coupled receptors in the mouse brain. PLoS One 7: e46304; PMCID: PMC3459911
- Gardner A, Jukkola P, & Gu C* (2012) Myelination of rodent hippocampal neurons in culture. Nature Protocols 7, 1774-1782; PMCID: PMC3536533
- Jukkola P, Lovett-Racke AE, Zamvil SS, & Gu C* (2012) K+ channel alterations in the progression of experimental autoimmune encephalomyelitis. Neurobiology of Disease 47, 280-293; PMCID: PMC3367054
- Gu YZ, Barry J, McDougle R, Terman D, & Gu C* (2012) Alternative splicing regulates Kv3.1 polarized targeting to adjust the maximal spiking frequency. The Journal of Biological Chemistry 287, 1755-1769; PMCID: PMC3265858
- Gu C*, & Barry J (2011) Function and mechanism of axonal targeting of voltage-sensitive potassium channels. Progress in Neurobiology 94, 115-132; PMCID: PMC3112463
- Gu C*, & Gu YZ (2011) Clustering and activity tuning of Kv1 channels in myelinated Hippocampal axons. The Journal of Biological Chemistry 286, 25835-25847; PMCID: PMC3138291
- Gu Y, & Gu C* (2010) Dynamics of Kv1 channel transport in axons. PLoS One 5, e11931; PMCID: PMC2915926
- Barry J, Gu Y, & Gu C* (2010) Polarized targeting of L1-CAM regulates axonal and dendritic bundling in vitro. European Journal of Neuroscience 32, 1618-1631; PMCID: PMC2981701
- Xu M, Gu YZ, Barry J, & Gu C* (2010) Kinesin I transports tetramerized Kv3 channels through the axon initial segment via direct binding. The Journal of Neuroscience 30, 15987-16001; PMCID: PMC2996050
- Xu M, Cao RF, Xiao R, Zhu M, & Gu C* (2007) The axon-dendrite targeting of Kv3 (Shaw) channels is determined by a conditional signal that associates with the T1 domain and ankyrin G. The Journal of Neuroscience 27, 14158-14170.
- Gu C*, Zhou W, Puthenveedu MA, Xu M, Jan YN, & Jan LY* (2006) The microtubule plus-end tracking protein EB1 is required for Kv1 voltage-gated K+ channel axonal targeting. Neuron 52, 803-816.
- Gu C, Jan YN, & Jan LY (2003) A conserved domain in axonal targeting of Kv1 (Shaker) voltage-gated potassium channels. Science 301, 646-649
- Gu C, Sorkin A, & Cooper DMF (2001) Persistent interactions of the two transmembrane clusters dictate targeting and functional assembly of adenylyl cyclase. Current Biology 11, 185-190