Proteolytic cleavage is required for functional neuroligin 2 maturation and trafficking in Drosophila

Journal of Molecular Cell Biology
Renjun TuWei Xie

Abstract

Neuroligins (Nlgs) are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroligin genes have been linked with some neurodevelopmental disorders such as autism. These mutated Nlgs are mostly retained in the endoplasmic reticulum (ER). However, the mechanisms underlying normal Nlg maturation and trafficking have remained largely unknown. Here, we found that Drosophila neuroligin 2 (DNlg2) undergoes proteolytic cleavage in the ER in a variety of Drosophila tissues throughout developmental stages. A region encompassing Y642-T698 is required for this process. The immature non-cleavable DNlg2 is retained in the ER and non-functional. The C-terminal fragment of DNlg2 instead of the full-length or non-cleavable DNlg2 is able to rescue neuromuscular junction defects and GluRIIB reduction induced by dnlg2 deletion. Intriguingly, the autism-associated R598C mutation in DNlg2 leads to similar marked defects in DNlg2 proteolytic process and ER export, revealing a potential role of the improper Nlg cleavage in autism pathogenesis. Collectively, our findings uncover a specific mechanism that controls DNlg2 maturation and trafficking via proteolytic cleavage in the ER, sug...Continue Reading

References

May 5, 1995·Cell·K IchtchenkoT C Südhof
Sep 5, 1997·Science·M IrieT C Südhof
Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·J L Vogel, T M Kristie
Nov 5, 2002·Journal of Cell Science·Hao XuWilliam S Trimble
Apr 2, 2003·Nature Genetics·Stéphane JamainUNKNOWN Paris Autism Research International Sibpair Study
May 21, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Davide ComolettiPalmer Taylor
Dec 20, 2005·The Journal of Biological Chemistry·Qiuming GongZhengfeng Zhou
Feb 27, 2007·Nature Genetics·UNKNOWN Autism Genome Project ConsortiumKacie J Meyer
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Johannes BischofKonrad Basler
Feb 28, 2008·The Journal of Comparative Neurology·Richard W DanielsAaron DiAntonio
Sep 4, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chen ZhangThomas C Südhof
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Nikolaos GiagtzoglouHugo J Bellen
Jul 10, 2010·The Journal of Biological Chemistry·Antonella De JacoPalmer Taylor
Jan 14, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mingkuan SunWei Xie
Aug 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Mark EthertonThomas C Südhof
Nov 1, 2011·Molecular Neurobiology·David KnightGabrielle L Boulianne
Sep 8, 2012·Molecular and Cellular Neurosciences·Brian A Mozer, David J Sandstrom
Oct 23, 2012·Neuron·Rui T PeixotoMichael D Ehlers
Oct 23, 2012·Neuron·Kunimichi SuzukiTakeshi Iwatsubo
Jun 26, 2013·Behavioural Brain Research·Nina HahnRalf Heinrich
Sep 27, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yi LiJunhai Han
Mar 19, 2014·The Journal of Cell Biology·Annamaria RuggianoPedro Carvalho
Sep 18, 2014·The Journal of Biological Chemistry·Guanglin XingWei Xie
Feb 15, 2015·Journal of Molecular Cell Biology·Rui Jiang
Apr 29, 2015·Cell·Humsa S VenkateshMichelle Monje
Sep 1, 2015·Frontiers in Cellular Neuroscience·Katherine ConantSeung T Lim
Feb 5, 2016·Experimental Cell Research·Jinjun QianWei Xie

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.

Cell Adhesion Molecules in the Brain

Cell adhesion molecules found on cell surface help cells bind with other cells or the extracellular matrix to maintain structure and function. Here is the latest research on their role in the brain.