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Homodimerization and isoform-specific heterodimerization of neuroligins.
- Source :
-
The Biochemical journal [Biochem J] 2012 Sep 01; Vol. 446 (2), pp. 321-30. - Publication Year :
- 2012
-
Abstract
- Neuroligins are postsynaptic adhesion proteins involved in the establishment of functional synapses in the central nervous system. In rodents, four genes give rise to neuroligins that function at distinct synapses, with corresponding neurotransmitter and subtype specificities. In the present study, we examined the interactions between the different neuroligins by isolating endogenous oligomeric complexes using in situ cross-linking on primary neurons. Examining hippocampal, striatal, cerebellar and spinal cord cultures, we found that neuroligins form constitutive dimers, including homomers and, most notably, neuroligin 1/3 heteromers. Additionally, we found that neuroligin monomers are specifically retained in the secretory pathway through a cellular quality control mechanism that involves the neuroligin transmembrane domain, ensuring that dimerization occurs prior to cell surface trafficking. Lastly, we identified differences in the dimerization capacity of autism-associated neuroligin mutants, and found that neuroligin 3 R471C mutants can form heterodimers with neuroligin 1. The pervasive nature of neuroligin dimerization indicates that the unit of neuroligin function is the dimer, and raises intriguing possibilities of distinct heterodimer functions, and of interactions between native and mutant neuroligins contributing to disease phenotypes.
- Subjects :
- Amino Acid Substitution
Animals
Autistic Disorder genetics
Autistic Disorder metabolism
Brain cytology
Brain embryology
COS Cells
Cell Adhesion Molecules, Neuronal chemistry
Cell Adhesion Molecules, Neuronal genetics
Cells, Cultured
Chlorocebus aethiops
Cricetinae
Cross-Linking Reagents chemistry
Dimerization
HEK293 Cells
Humans
Membrane Proteins chemistry
Membrane Proteins genetics
Mice
Mutant Proteins chemistry
Mutant Proteins metabolism
Nerve Tissue Proteins chemistry
Nerve Tissue Proteins genetics
Neurons cytology
Protein Isoforms chemistry
Protein Isoforms genetics
Protein Isoforms metabolism
Protein Multimerization
Recombinant Fusion Proteins chemistry
Recombinant Fusion Proteins metabolism
Spinal Cord cytology
Spinal Cord embryology
Cell Adhesion Molecules, Neuronal metabolism
Membrane Proteins metabolism
Nerve Tissue Proteins metabolism
Neurons metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8728
- Volume :
- 446
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 22671294
- Full Text :
- https://doi.org/10.1042/BJ20120808