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Impaired AMPA receptor trafficking by a double knockout of zebrafish olfactomedin1a/b
Author(s) -
Nakaya Naoki,
Sultana Afia,
Tomarev Stanislav I.
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14231
Subject(s) - biology , ampa receptor , microbiology and biotechnology , palmitoylation , null allele , lipid microdomain , glutamate receptor , receptor , biochemistry , mutant , gene , cysteine , enzyme , membrane
The olfm1a and olfm1b genes in zebrafish encode conserved secreted glycoproteins. These genes are preferentially expressed in the brain and retina starting from 16 h post‐fertilization until adulthood. Functions of the Olfm1 gene is still unclear. Here, we produced and analyzed a null zebrafish mutant of both olfm1a and olfm1b genes ( olfm1 null). olfm1 null fish were born at a normal Mendelian ratio and showed normal body shape and fertility as well as no visible defects from larval stages to adult. Olfm1 proteins were preferentially localized in the synaptosomes of the adult brain. Olfm1 co‐immunoprecipitated with GluR2 and soluble NSF attachment protein receptor complexes indicating participation of Olfm1 in both pre‐ and post‐synaptic events. Phosphorylation of GluR2 was not changed while palmitoylation of GluR2 was decreased in the brain synaptosomal membrane fraction of olfm1 null compared with wt fish. The levels of GluR2, SNAP 25, flotillin1, and VAMP 2 were markedly reduced in the synaptic microdomain of olfm1 null brain compared with wt. The internalization of GluR2 in retinal cells and the localization of VAMP 2 in brain synaptosome were modified by olfm1 null mutation. This indicates that Olfm1 may regulate receptor trafficking from the intracellular compartments to the synaptic membrane microdomain, partly through the alteration of post‐translational GluR2 modifications such as palmitoylation. Olfm1 may be considered a novel regulator of the composition and function of the α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptor complex.