Neuroligin-Neurexin Interaction: Difference between revisions

====Mutations Leading To Neurodevelopmental Disorders====

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Several <scene name='Neuroligin-Neurexin_Interaction/Mutation_dimer/3'>point mutations</scene> (R437C (451 in NLGN 3), G99S, K378R, & V403M) within NLGN have been positively linked with Autism Spectrum Disorders. Although these mutations are remote from the NLGN-NRXN interface, conclusions can be drawn as to their impact on the function of NLGN. <scene name='Neuroligin-Neurexin_Interaction/Mutation_437/1'>Arg437Cys</scene>, a mutation shown to result in “savant” like attributes in mice, is believed to increase retention of NLGN in the endoplasmic reticulum preventing correct positioning at the cell surface. It could also disrupt a <scene name='Neuroligin-Neurexin_Interaction/Mutation_437_network/1'>dense network of charged residues</scene> (Asp 388, Asp 486, Glu 434, and Lys 338) through Trp 484, which are believed to be important for processing events.  <scene name='Neuroligin-Neurexin_Interaction/Mutation_403/1'>Val403Met</scene> is believed to affect correct folding of the C-terminal domain of NLGN and prevent formation of the functional dimer. The <scene name='Neuroligin-Neurexin_Interaction/Mutation_378/1'>Lys378Arg mutation</scene> which interacts with the <scene name='Neuroligin-Neurexin_Interaction/Mutation_378_interaction/2'>Cys-loop Asp 122</scene> through Van der Waals contacts could disrupt the Cys-loop reducing NLGN structural integrity. These mutations do not entirely disrupt NLGNs interaction with NRXN, but do impact NLGN in the subtle ways from which [[Neurodevelopmental Disorders|autism]] likely arises.<ref name="Fabrichny"/>  

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