Glutamatergic synapses exhibit significant molecular diversity, but circuit-specific mechanisms that underlie synaptic regulation are not well characterized. Prior reports show that Rho-guanine nucleotide exchange factor (RhoGEF) Tiam1 regulates perforant path→dentate gyrus granule neuron synapses. In the present study, we report Tiam1's homolog Tiam2 is implicated in glutamatergic neurotransmission in CA1 pyramidal neurons. We find that Tiam2 regulates evoked excitatory glutamatergic currents via a postsynaptic mechanism mediated by the catalytic Dbl-homology domain. Overall, we present evidence for RhoGEF Tiam2's role in glutamatergic synapse function at Schaffer collateral→CA1 pyramidal neuron synapses.
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http://dx.doi.org/10.1523/ENEURO.0500-21.2024 | DOI Listing |
Pharmacol Rep
October 2024
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
Background: Dendritic spine dysfunction is a key feature of Alzheimer's disease (AD) pathogenesis. Human T-cell lymphoma invasion and metastasis 2 (TIAM2) is expressed in two isoforms, the full length (TIAM2L) and a short transcript (TIAM2S). Compared to TIAM2L protein, which is undetectable, TIAM2S protein is abundant in human brain tissue, especially the hippocampus, and can promote neurite outgrowth in our previous findings.
View Article and Find Full Text PDFeNeuro
July 2024
Department of Biological Sciences, Neurobiology Section, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California 90089
Glutamatergic synapses exhibit significant molecular diversity, but circuit-specific mechanisms that underlie synaptic regulation are not well characterized. Prior reports show that Rho-guanine nucleotide exchange factor (RhoGEF) Tiam1 regulates perforant path→dentate gyrus granule neuron synapses. In the present study, we report Tiam1's homolog Tiam2 is implicated in glutamatergic neurotransmission in CA1 pyramidal neurons.
View Article and Find Full Text PDFCell Rep
May 2024
Dynamical Cell Systems Group, Division of Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. Electronic address:
How cancer cells determine their shape in response to three-dimensional (3D) geometric and mechanical cues is unclear. We develop an approach to quantify the 3D cell shape of over 60,000 melanoma cells in collagen hydrogels using high-throughput stage-scanning oblique plane microscopy (ssOPM). We identify stereotypic and environmentally dependent changes in shape and protrusivity depending on whether a cell is proximal to a flat and rigid surface or is embedded in a soft environment.
View Article and Find Full Text PDFFront Immunol
December 2023
Signalling Programme, Babraham Institute, Cambridge, United Kingdom.
Rac GTPases are required for neutrophil adhesion and migration, and for the neutrophil effector responses that kill pathogens. These Rac-dependent functions are impaired when neutrophils lack the activators of Rac, Rac-GEFs from the Prex, Vav, and Dock families. In this study, we demonstrate that Tiam1 is also expressed in neutrophils, governing focal complexes, actin cytoskeletal dynamics, polarisation, and migration, in a manner depending on the integrin ligand to which the cells adhere.
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November 2021
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
Despite the undisputable role of the small GTPase Rac1 in the regulation of actin cytoskeleton reorganization, the Rac guanine-nucleotide exchange factors (Rac-GEFs) involved in Rac1-mediated motility and invasion in human lung adenocarcinoma cells remain largely unknown. Here, we identify FARP1, ARHGEF39, and TIAM2 as essential Rac-GEFs responsible for Rac1-mediated lung cancer cell migration upon EGFR and c-Met activation. Noteworthily, these Rac-GEFs operate in a non-redundant manner by controlling distinctive aspects of ruffle dynamics formation.
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