Leo Sher, M.D.

The article, “The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors” by Jeffrey N. Savas, Luís F. Ribeiro, Keimpe D. Wierda, Rebecca Wright, Laura A. DeNardo-Wilke, Heather C. Rice, Ingrid Chamma, Yi-Zhi Wang, Roland Zemla, Mathieu Lavallée-Adam, Kristel M. Vennekens, Matthew L. O’Sullivan, Joseph K. Antonios, Elizabeth A. Hall, Olivier Thoumine, Alan D. Attie, John R. Yates III,  Anirvan Ghosh,  and Joris de Wit has just been published in “Neuron” (1).

Our brain consists of billions of neurons.  Neurons can be described as morphologic and functional units of the nervous system, consisting of the nerve cell body with its dendrites and axon.During brain development, neurons connect with other neurons through cell-cell contacts called synapses. Receptors are essential components of the synaptic proteome. Their dynamic trafficking is a crucial element underlying the function and plasticity of synapses. Genetic analysis of humans has shown that mutations in genes involved in synaptic communication can be involved in neuropsychiatric and neurological diseases such as Alzheimer’s disease (2,3).

In this paper (1), the two research groups reported that they found a new pathway that regulates the proper sorting of many essential synaptic proteins in neurons. Disruption of this sorting pathway in neuropsychiatric and neurological conditions severely impedes the efficient communication between neurons. The study emphasizes the importance of proper synaptic protein sorting.  Reduced synaptic activity might result in synapse loss and neuronal degeneration. To read the abstract of the article, please click here.

References
1. Savas JN, Ribeiro LF, Wierda KD, Wright R, DeNardo-Wilke LA, Rice HC, Chamma I, Wang YZ, Zemla R, Lavallée-Adam M, Vennekens KM, O’Sullivan ML, Antonios JK, Hall EA, Thoumine O, Attie AD, Yates JR 3rd, Ghosh A, de Wit J. The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors. Neuron. 2015 Aug 19;87(4):764-80.
2. Grupe A, Li Y, Rowland C, Nowotny P, Hinrichs AL, Smemo S, Kauwe JS, Maxwell TJ, Cherny S, Doil L, Tacey K, van Luchene R, Myers A, Wavrant-De Vrièze F, Kaleem M, Hollingworth P, Jehu L, Foy C, Archer N, Hamilton G, Holmans P, Morris CM, Catanese J, Sninsky J, White TJ, Powell J, Hardy J, O’Donovan M, Lovestone S, Jones L, Morris JC, Thal L, Owen M, Williams J, Goate A. A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. Am J Hum Genet. 2006 Jan;78(1):78-88.
3. Overton JD, Bjornson RD, Carriero NJ, Meyer KA, Bilguvar K, Mane SM, Sestan N, Lifton RP, Günel M, Roeder K, Geschwind DH, Devlin B, State MW. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012 Apr 4;485(7397):237-41.