RGD Reference Report - Identification and characterization of a synaptojanin 2 splice isoform predominantly expressed in nerve terminals. - Rat Genome Database

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Identification and characterization of a synaptojanin 2 splice isoform predominantly expressed in nerve terminals.

Authors: Nemoto, Y  Wenk, MR  Watanabe, M  Daniell, L  Murakami, T  Ringstad, N  Yamada, H  Takei, K  De Camilli, P 
Citation: Nemoto Y, etal., J Biol Chem 2001 Nov 2;276(44):41133-42.
RGD ID: 628465
Pubmed: PMID:11498538   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M106404200   (Journal Full-text)

We have previously identified synaptojanin 1, a phosphoinositide phosphatase predominantly expressed in the nervous system, and synaptojanin 2, a broadly expressed isoform. Synaptojanin 1 is concentrated in nerve terminals, where it has been implicated in synaptic vesicle recycling and actin function. Synaptojanin 2A is targeted to mitochondria via a PDZ domain-mediated interaction. We have now characterized an alternatively spliced form of synaptojanin 2 that shares several properties with synaptojanin 1. This isoform, synaptojanin 2B, undergoes further alternative splicing to generate synaptojanin 2B1 and 2B2. Both amphiphysin and endophilin, two partners synaptojanin 1, bind synaptojanin 2B2, whereas only amphiphysin binds synaptojanin 2B1. Sequence similar to the endophilin-binding site in synaptojanin 1 is present only in synaptojanin 2B2, and this sequence was capable of affinity purifying endophilin from rat brain. The Sac1 domain of synaptojanin 2 exhibited phosphoinositide phosphatase activity very similar to that of the Sac1 domain of synaptojanin 1. Site-directed mutagenesis further illustrated its functional similarity to the catalytic domain of Sac1 proteins. Antibodies raised against the synaptojanin 2B-specific carboxyl-terminal region identified a 160-kDa protein in brain and testis. Immunofluorescence showed that synaptojanin 2B is localized at nerve terminals in brain and at the spermatid manchette in testis. Active Rac1 GTPase affects the intracellular localization of synaptojanin 2, but not of synaptojanin 1. These results suggest that synaptojanin 2B has a partially overlapping function with synaptojanin 1 in nerve terminals, with additional roles in neurons and other cells including spermatids.

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Amph  (amphiphysin)
Sh3gl1  (SH3 domain containing GRB2 like 1, endophilin A2)
Sh3gl2  (SH3 domain containing GRB2 like 2, endophilin A1)
Synj1  (synaptojanin 1)
Synj2  (synaptojanin 2)
Synj2_v1  (synaptojanin 2, variant 1)
Synj2_v2  (synaptojanin 2, variant 2)
Synj2_v3  (synaptojanin 2, variant 3)
Synj2bp  (synaptojanin 2 binding protein)

Objects referenced in this article
Gene Kcnip2_v1 potassium voltage-gated channel interacting protein 2, variant 1 Rattus norvegicus
Gene Kcnip2_v2 potassium voltage-gated channel interacting protein 2, variant 2 Rattus norvegicus
Gene Sh3gl3 SH3 domain containing GRB2 like 3, endophilin A3 Rattus norvegicus

Additional Information