Jian Cheng Tu
Johns Hopkins University School of Medicine
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Featured researches published by Jian Cheng Tu.
Neuron | 1999
Jian Cheng Tu; Bo Xiao; Scott Naisbitt; Joseph P. Yuan; Ronald S. Petralia; Paul R. Brakeman; Andrew Doan; Vinay K. Aakalu; Anthony Lanahan; Morgan Sheng; Paul F. Worley
Shank is a recently described family of postsynaptic proteins that function as part of the NMDA receptor-associated PSD-95 complex (Naisbitt et al., 1999 [this issue of Neuron]). Here, we report that Shank proteins also bind to Homer. Homer proteins form multivalent complexes that bind proline-rich motifs in group 1 metabotropic glutamate receptors and inositol trisphosphate receptors, thereby coupling these receptors in a signaling complex. A single Homer-binding site is identified in Shank, and Shank and Homer coimmunoprecipitate from brain and colocalize at postsynaptic densities. Moreover, Shank clusters mGluR5 in heterologous cells in the presence of Homer and mediates the coclustering of Homer with PSD-95/GKAP. Thus, Shank may cross-link Homer and PSD-95 complexes in the PSD and play a role in the signaling mechanisms of both mGluRs and NMDA receptors.
Neuron | 1999
Scott Naisbitt; Eunjoon Kim; Jian Cheng Tu; Bo Xiao; Carlo Sala; Juli G. Valtschanoff; Richard J. Weinberg; Paul F. Worley; Morgan Sheng
NMDA receptors are linked to intracellular cytoskeletal and signaling molecules via the PSD-95 protein complex. We report a novel family of postsynaptic density (PSD) proteins, termed Shank, that binds via its PDZ domain to the C terminus of PSD-95-associated protein GKAP. A ternary complex of Shank/GKAP/PSD-95 assembles in heterologous cells and can be coimmunoprecipitated from rat brain. Synaptic localization of Shank in neurons is inhibited by a GKAP splice variant that lacks the Shank-binding C terminus. In addition to its PDZ domain, Shank contains a proline-rich region that binds to cortactin and a SAM domain that mediates multimerization. Shank may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD-95 complexes and coupling them to regulators of the actin cytoskeleton.
Neuron | 1998
Bo Xiao; Jian Cheng Tu; Ronald S. Petralia; Joseph P. Yuan; Andrew Doan; Christopher D Breder; Alicia Ruggiero; Anthony Lanahan; Robert J. Wenthold; Paul F. Worley
Homer is a neuronal immediate early gene (IEG) that is enriched at excitatory synapses and binds group 1 metabotropic glutamate receptors (mGluRs). Here, we characterize a family of Homer-related proteins derived from three distinct genes. Like Homer IEG (now termed Homer 1a), all new members bind group 1 mGluRs. In contrast to Homer 1a, new members are constitutively expressed and encode a C-terminal coiled-coil (CC) domain that mediates self-multimerization. CC-Homers form natural complexes that cross-link mGluRs and are enriched at the postsynaptic density. Homer 1a does not multimerize and blocks the association of mGluRs with CC-Homer complexes. These observations support a model in which the dynamic expression of Homer 1a competes with constitutively expressed CC-Homers to modify synaptic mGluR properties.
Current Opinion in Neurobiology | 2000
Bo Xiao; Jian Cheng Tu; Paul F. Worley
The proteins of the Homer family bind to proline-rich sequences in group I metabotropic glutamate receptors, inositol trisphosphate receptors, ryanodine receptors, and Shank family proteins. Homer proteins also self associate and function as adaptors to couple interacting proteins. Recent observations indicate a role for Homer complexes in signal transduction, synaptogenesis and receptor trafficking.
The Journal of Neuroscience | 2000
Paul J. Kammermeier; Bo Xiao; Jian Cheng Tu; Paul F. Worley; Stephen R. Ikeda
Group I metabotropic glutamate receptors (mGluR1 and 5) couple to intracellular calcium pools by a family of proteins, termed Homer, that cross-link the receptor to inositol trisphosphate receptors. mGluRs also couple to membrane ion channels via G-proteins. The role of Homer proteins in channel modulation was investigated by expressing mGluRs and various forms of Homer in rat superior cervical ganglion (SCG) sympathetic neurons by intranuclear cDNA injection. Expression of cross-linking-capable forms of Homer (Homer 1b, 1c, 2, and 3, termed long forms) occluded group I mGluR-mediated N-type calcium and M-type potassium current modulation. This effect was specific for group I mGluRs. mGluR2 (group II)-mediated inhibition of N-channels was unaltered. Long forms of Homer decreased modulation of N- and M-type currents but did not selectively block distinct G-protein pathways. Short forms of Homer, which cannot self-multimerize (Homer 1a and a Homer 2 C-terminal deletion), did not alter mGluR–ion channel coupling. When coexpressed with long forms of Homer, short forms restored the mGluR1a-mediated calcium current modulation in an apparent dose-dependent manner. Homer 2b induced cell surface clusters of mGluR5 in SCG neurons. Conversely, a uniform distribution was observed when mGluR5 was expressed alone or with Homer short forms. These studies indicate that long and short forms of Homer compete for binding to mGluRs and regulate their coupling to ion channels. In vivo, the immediate early Homer 1a is anticipated to enhance ion channel modulation and to disrupt coupling to releasable intracellular calcium pools. Thus, Homer may regulate the magnitude and predominate signaling output of group I mGluRs.
Neuron | 2000
Jutta Beneken; Jian Cheng Tu; Bo Xiao; Mutsuo Nuriya; Joseph P. Yuan; Paul F. Worley; Daniel J. Leahy
Homer EVH1 (Ena/VASP Homology 1) domains interact with proline-rich motifs in the cytoplasmic regions of group 1 metabotropic glutamate receptors (mGluRs), inositol-1,4,5-trisphosphate receptors (IP3Rs), and Shank proteins. We have determined the crystal structure of the Homer EVH1 domain complexed with a peptide from mGluR (TPPSPF). In contrast to other EVH1 domains, the bound mGluR ligand assumes an unusual conformation in which the side chains of the Ser-Pro tandem are oriented away from the Homer surface, and the Phe forms a unique contact. This unusual binding mode rationalizes conserved features of both Homer and Homer ligands that are not shared by other EVH1 domains. Site-directed mutagenesis confirms the importance of specific Homer residues for ligand binding. These results establish a molecular basis for understanding the biological properties of Homer-ligand complexes.
Molecular and Cellular Neuroscience | 2002
Fabrice Ango; David Robbe; Jian Cheng Tu; Bo Xiao; Paul F. Worley; Jean-Philippe Pin; Joël Bockaert; Laurent Fagni
The metabotropic glutamate (mGlu) receptors are a family of receptors involved in the tuning of fast excitatory synaptic transmission in the brain. Experiments performed in heterologous expression systems suggest that cell surface expression of group I mGlu receptors is controlled by their auxiliary protein, Homer. However, whether or not this also applies to neurons remains controversial. Here we show that in cultured cerebellar granule cells, the group I mGlu receptor subtype, mGlu5, transfected alone is functionally expressed at the surface of these neurons. Transfected Homer1b caused intracellular retention and clustering of this receptor at synaptic sites. Recombinant Homer1a alone did not affect cell surface expression of the receptor, but in neurons transfected with Homer1b, excitation-induced expression of native Homer1a reversed the intracellular retention of mGlu5 receptors, resulting in the receptor trafficking to synaptic membranes. Transfected Homer1a also increased the latency and amplitude of the mGlu5 receptor Ca2+ response. These results indicate that Homer1 proteins regulate synaptic cycling and Ca2+ signaling of mGlu5 receptors, in response to neuronal activity.
Cell | 2013
M. Ali Bangash; Joo Min Park; Tatiana Melnikova; Dehua Wang; Soo Kyeong Jeon; Deidre Lee; Sbaa Syeda; Juno Kim; Mehreen Kouser; Joshua Schwartz; Yiyuan Cui; Xia Zhao; Haley E. Speed; Sara E. Kee; Jian Cheng Tu; Jia Hua Hu; Ronald S. Petralia; David J. Linden; Craig M. Powell; Alena V. Savonenko; Bo Xiao; Paul F. Worley
Our paper reported an analysis of a mouse genetic model that deletes the C terminus of Shank3 to mimic human mutations that cause autism spectrum disorder. Figure panels for several polyubiquitination assays were improperly assembled, leading to multiple repetitions of bands in western blots of the lysates. These errors did not affect the quantitative analysis of polyubiquitination because this analysis was performed as described and was not dependent on representative western blot images. In light of the figure preparation issues, we feel that the most responsible course of action is to retract the paper. We sincerely apologize to the scientific community for any misunderstanding that these errors may have caused.
Neuron | 1998
Jian Cheng Tu; Bo Xiao; Joseph P. Yuan; Anthony Lanahan; Kathleen Leoffert; Min Li; David J. Linden; Paul F. Worley
Cell | 2011
M. Ali Bangash; Joo Min Park; Tatiana Melnikova; Dehua Wang; Soo Kyeong Jeon; Deidre Lee; Sbaa Syeda; Juno Kim; Mehreen Kouser; Joshua Schwartz; Yiyuan Cui; Xia Zhao; Haley E. Speed; Sara E. Kee; Jian Cheng Tu; Jia Hua Hu; Ronald S. Petralia; David J. Linden; Craig M. Powell; Alena V. Savonenko; Bo Xiao; Paul F. Worley