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

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

Cell reports (2019-12-05)
Jeremiah D Paskus, Chen Tian, Erin Fingleton, Christine Shen, Xiaobing Chen, Yan Li, Samuel A Myers, John D Badger, Michael A Bemben, Bruce E Herring, Katherine W Roche
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Phosphatase Inhibitor Cocktail 3, DMSO solution
Sigma-Aldrich
Phosphatase Inhibitor Cocktail 2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
Sigma-Aldrich
Monoclonal Anti-Glun2A/Nr2A antibody produced in mouse, clone S327-95, purified immunoglobulin
Sigma-Aldrich
IgG, Rabbit, Rabbit IgG Polyclonal Antibody validated for use in ELISA.
Sigma-Aldrich
Anti-Kalirin Antibody, Upstate®, from rabbit