High impact information on EXOC4

• We have found that two components of the exocyst complex, Sec8 and Exo70, separately control synaptic targeting and insertion of AMPA-type glutamate receptors [1].
• In linear sucrose gradients, Sem1p cosedimented with the exocyst component Sec8p [2].
• The assembly of this complex also requires the PDZ domain protein SAP97, a member of the MAGUKs family, which binds to Sec8 upon its translocation to the lipid raft [3].
• CONCLUSION: Our locus-wide association and LD analyses identified intronic SNPs and haplotypes in the SEC8L1 gene that are strongly associated with RA [4].
• Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a subunit of the exocyst complex, and rheumatoid arthritis in a Japanese population [4].

Biological context of EXOC4

• We observed that one of the subunits in the sec6/8 or exocyst complex, sec8, contains a C-terminal consensus sequence for PDZ binding [5].
• The SEC8L1 SNPs with significant allele associations were all located in a single conserved LD block (block 4) [4].
• One likely activity of these proteins is to protect the cohesin subunit Rec8 from cleavage at the metaphase I-anaphase I transition [6].
• REC8 is a master regulator of chromatin structure and function during meiosis [7].
• Alleles of afd1 dissect REC8 functions during meiotic prophase I [7].

Anatomical context of EXOC4

• Immunofluorescence staining of COS cells cotransfected with hSec10p and a mammalian Sec8p demonstrates that these two proteins have an identical distribution in the cell including a localization in the peripheral cytoplasm [8].
• A role for Sec8 in oligodendrocyte morphological differentiation [9].
• These results suggest that Sec8 plays a central role in oligodendrocyte membrane formation by regulating the recruitment of vesicles that transport myelin proteins such as OSP/Claudin11 to sites of membrane growth [9].
• The meiotic cohesin REC8 was also found to be up-regulated after irradiation, linking sister chromatid centromeres in the metaphase-arrested and subsequent giant cells [10].
• We show that REC8 has an essential role in mammalian meiosis, in that Rec8 null mice of both sexes have germ cell failure and are sterile [11].

Associations of EXOC4 with chemical compounds

• In addition, binding of sec8 is dependent on its C-terminal-binding sequence namely Thr-Thr-Val (TTV) [5].

Other interactions of EXOC4

• Expression of AP-1B (but not AP-1A) enhanced the recruitment of at least two subunits of the exocyst complex (Sec8 and Exo70) required for basolateral transport [12].
• At the basolateral membrane of ADPKD cells, there was a notable loss of the exocyst components sec6/sec8 and an unidentified syntaxin [13].
• We demonstrate that oligodendrocytes express several key molecules necessary for the targeting of transport vesicles to areas of rapid membrane growth, including the exocyst components Sec8 and Sec6 and the multidomain scaffolding proteins CASK and Mint1 [9].
• RT-PCR demonstrated chimeric transcripts containing the first 11 exons of SEC8L1 fused to exon 3 of PTEN [14].
• Real-time quantitative polymerase chain reaction revealed that SEC8L1 was expressed ubiquitously in human tissues, including fibroblast-like synoviocytes from RA patients [4].

References