SYNCRIP, a Cytoplasmic Counterpart of Heterogeneous Nuclear Ribonucleoprotein R, Interacts with Ubiquitous Synaptotagmin Isoforms

Abstract

Synaptotagmins (Syts) are a large family of membrane proteins consisted of at least 12 isoforms. They are categorized in neuron-specific isoforms (I-V, X, and XI) and ubiquitous isoforms (VI-IX) based on their expression patterns. Syt-I, a neuron-specific and abundant isoform, has been well characterized and postulated to be the exocytotic Ca 2؉ sensor. However, the functions of other isoforms remain obscure. Here, we report that ubiquitous isoforms of synaptotagmins, Syt-VII, Syt-VIII, and Syt-IX, interacted with a cytoplasmic RNA-binding protein, SYNCRIP (Synaptotagmin-binding, cytoplasmic RNA-interacting protein), through their C2B domains. SYNCRIP was originally found in the Syt-II C2AB domain bound fraction from the mouse brain lysate. cDNA cloning of SYNCRIP cDNA revealed that the protein was highly homologous to heterogeneous nuclear ribonucleoprotein R (hnRNP R) recently identified. SYNCRIP protein was ubiquitously and constantly expressed in various tissues of mice parallel to hnRNP R. SYNCRIP indeed bound RNA with preference to poly(A) RNA; however, in contrast to the nuclear localization of hnRNP R, SYNCRIP was distributed predominantly in the cytoplasm as judged by both biochemical fractionation and immunohistochemical studies. In vitro binding experiments showed the potential interaction of SYNCRIP with C2B domains of Syts except for those of Syt-V, -VI, and -X. Furthermore, the interaction between SYNCRIP and Syt-VII, -VIII, or -IX was revealed by coimmunoprecipitation experiments using COS cells transiently expressing each Syt isoform. These findings suggested that SYNCRIP was a target of ubiquitous type of Syts and implied the involvement of ubiquitous Syts in the regulation of dynamics of the cytoplasmic mRNA.

Synaptotagmin 11 interacts with components of the RNA‐induced silencing complex RISC in clonal pancreatic β‐cells

“…The involvement of synaptotagmin in the regulation of mRNA dynamics is not without precedence. The cytoplasmic RNA binding-protein SYNCRIP interacts with the C 2 B domains of several syts including syt11, but not syt4 thus suggesting functional differences between the two paralogs [40]. The novel interaction of syt11 with the ancestral staphylococcal nuclease domain-containing 1 protein SND1 is of particular interest.…”

Molecular Characterization of Chronic-type Adult T-cell Leukemia/Lymphoma

“…We also identified SYNCRIP as a common MCR in both types of ATL. SYNCRIP is a gene known to be involved in maturation of mRNA (29). RXRA, which has been reported to be implicated in colorectal carcinogenesis (30), is also frequently altered in both types of ATL.…”

Hyperphosphorylated C-terminal Repeat Domain-associating Proteins in the Nuclear Proteome Link Transcription to DNA/Chromatin Modification and RNA Processing

“…NSAP1 has more recently been identified as one of three splice variants of hnRNP Q (42) (other synonyms for Q splice variants are SYNCRIP and GRY-RBP; Refs. [42][43][44]. Remarkably, hnRNP Q proteins have been found to bind to SMN protein, mutations in which cause spinal muscular atrophy (42,98) probably by disturbing spliceosome formation and splicing.…”

“…Although NSAP1 was first identified as a protein that binds the NS1 protein of minute virus of mice (41), it has more recently been identified as one of three splice variants of hnRNP Q (42) (other synonyms for Q splice variants are SYNCRIP and GRY-RBP; Refs. [42][43][44]. We obtained antibodies against NSAP1 and used them to test the assigned identity of the phosphoCTDbinding protein.…”