Structural and Functional Deficits in a Neuronal Calcium Sensor-1 Mutant Identified in a Case of Autistic Spectrum Disorder
| Autor: | Lee P. Haynes, Mark T. W. Handley, Lu-Yun Lian, Robert D. Burgoyne |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Magnetic Resonance Spectroscopy
Cell Biology/Neuronal Signaling Mechanisms Neuronal Calcium-Sensor Proteins Mutant Intracellular Space lcsh:Medicine medicine.disease_cause behavioral disciplines and activities Cell Biology/Cell Signaling Mice Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine mental disorders medicine Animals Humans Missense mutation Calcium Signaling Autistic Disorder lcsh:Science 030304 developmental biology Calcium signaling 0303 health sciences Mutation Multidisciplinary biology Point mutation Cell Membrane Neuropeptides lcsh:R Transport protein Cell biology Protein Transport Amino Acid Substitution Biochemistry Neuronal calcium sensor-1 Membrane protein Cell Biology/Neuronal and Glial Cell Biology biology.protein Calcium Mutant Proteins lcsh:Q Interleukin-1 Receptor Accessory Protein 030217 neurology & neurosurgery Research Article Protein Binding trans-Golgi Network |
| Zdroj: | PLoS ONE, Vol 5, Iss 5, p e10534 (2010) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0010534 |
| Popis: | Neuronal calcium sensor-1 (NCS-1) is a Ca(2+) sensor protein that has been implicated in the regulation of various aspects of neuronal development and neurotransmission. It exerts its effects through interactions with a range of target proteins one of which is interleukin receptor accessory protein like-1 (IL1RAPL1) protein. Mutations in IL1RAPL1 have recently been associated with autism spectrum disorders and a missense mutation (R102Q) on NCS-1 has been found in one individual with autism. We have examined the effect of this mutation on the structure and function of NCS-1. From use of NMR spectroscopy, it appeared that the R102Q affected the structure of the protein particularly with an increase in the extent of conformational exchange in the C-terminus of the protein. Despite this change NCS-1(R102Q) did not show changes in its affinity for Ca(2+) or binding to IL1RAPL1 and its intracellular localisation was unaffected. Assessment of NCS-1 dynamics indicated that it could rapidly cycle between cytosolic and membrane pools and that the cycling onto the plasma membrane was specifically changed in NCS-1(R102Q) with the loss of a Ca(2+) -dependent component. From these data we speculate that impairment of the normal cycling of NCS-1 by the R102Q mutation could have subtle effects on neuronal signalling and physiology in the developing and adult brain. |
| Databáze: | OpenAIRE |
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