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Publication : Synaptic Kalirin-7 and Trio Interactomes Reveal a GEF Protein-Dependent Neuroligin-1 Mechanism of Action.

First Author  Paskus JD Year  2019
Journal  Cell Rep Volume  29
Issue  10 Pages  2944-2952.e5
PubMed ID  31801062 Mgi Jnum  J:298861
Mgi Id  MGI:6489167 Doi  10.1016/j.celrep.2019.10.115
Citation  Paskus JD, et al. (2019) Synaptic Kalirin-7 and Trio Interactomes Reveal a GEF Protein-Dependent Neuroligin-1 Mechanism of Action. Cell Rep 29(10):2944-2952.e5
abstractText  The RhoGEFs Kalirin-7 and Trio are regulators of synaptic plasticity, and their dysregulation is associated with a range of neurodevelopmental and neurodegenerative disorders. Although studies have implicated both Kalirin and Trio in certain diseases, such as tauopathies, they remarkably differ in their association with other disorders. Using unbiased proteomics, we identified interactomes of Kalirin-7 and Trio to ascertain distinct protein association networks associated with their respective function and revealed groups of proteins that preferentially interact with a particular RhoGEF. In comparison, we find Trio interacts with a range of axon guidance and presynaptic complexes, whereas Kalirin-7 associates with several synaptic adhesion molecules. Specifically, we show Kalirin-7 is an interactor of the cell adhesion molecule neuroligin-1 (NLGN1), and NLGN1-dependent synaptic function is mediated through Kalirin-7 in an interaction-dependent manner. Our data reveal not only the interactomes of two important disease-related proteins, but also provide an intracellular effector of NLGN1 function.
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