title: Leucine-rich glioma inactivated 3 associates with syntaxin 1.
abstract: Leucine-rich glioma inactivated 3 (LGI3) is a member of LGI/epitempin (EPTP) family. The biological function of LGI3 and its association with disease are not known. We previously reported that mouse LGI3 was highly expressed in brain in a developmentally and transcriptionally regulated manner. In this study, we identified syntaxin 1, a SNARE component in exocytosis, as a candidate functional target of LGI3. Western blot analysis of mouse brain extract with LGI3 antibodies detected multiple protein forms (75-, 60-, 35- and 25-kDa). Proteomic analysis, pull-down and coimmunoprecipitation experiments identified syntaxin 1 as an LGI3-associated protein. LGI3 colocalized with syntaxin 1 in processes of cortical neurons with punctate synaptic pattern and was enriched in synaptosomal fraction. Coimmunoprecipitation showed that LGI3-syntaxin 1 complex did not contain other SNARE components, SNAP25 and VAMP2. Recombinant LGI3 attenuated Ca(2+)-evoked glutamate release from digitonin-permeabilized synaptosomes and transfection of PC12 cells with LGI3 decreased K(+)-induced secretion of human growth hormone. Thus, LGI3 may play a regulatory role in neuronal exocytosis via its interaction with syntaxin 1.
authors.affiliation: Department of Biochemistry, College of Medicine, Chung-Ang University, 221 Heuksuk-dong, Dongjak-koo, Seoul 156-756, Republic of Korea.
authors.forename: Woo-Jae
authors.initials: WJ
authors.lastname: Park
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Nyoun Soo
authors.initials: NS
authors.lastname: Kwon
authors.forename: Kwang Jin
authors.initials: KJ
authors.lastname: Baek
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Yun