Role of LMAN1 (Ergic‐53) in the trafficking of GABAARs

Abstract

LMAN1, also called as ERGIC 53, is known as a cargo receptor that gathers mainly in the tubulovesicular cluster, also referred as ER‐to‐Golgi intermediate compartment (ERGIC), and recycles between ER and Golgi in a COPII and COPI dependent pathways (Hauri, Kappeler et al. 2000). Its C terminus contains a diphenylalanine motif that binds to COPII coat and facilitates the anterograde transport and a dilysine motif that binds to COPI coat and mediates the retrograde transport (Khoriaty, Vasievich et al. 2012). LMAN1 recognizes and binds to the high mannose structure on the glycoprotein through its luminal carbohydrate recognition domain (CRD) (Zheng, Liu et al. 2010). LMAN1 is the known specific cargo receptor for factor V and factor VIII, cathepsin C, cathepsin Z and α1‐antitrypsin (Hauri, Kappeler et al. 2000, Zheng, Liu et al. 2010).Our lab's initial mass spec data shows that LMAN1 is one of the molecules that interact with GABAARs. We hypothesize that LMAN1 is a trafficking factor for GABAARS receptors. We have several new findings: firstly, endogenous LMAN1 interacts with at least α1 subunits in HEK293T cells overexpressed with WT GABAARs. This interaction is not dependent on the glycosylation status of α1 subunits. And the carbohydrate recognition domain (CRD) of LMAN1 is critical in the interaction between α1 subunits and LMAN1. Secondly, knocking‐down of LMAN1 in mouse hypothalamic GnRH neuronal (GT17) cells negatively affected the surface expression level of endogenous α1 and β3 subunits. We conclude that LMAN1 is also a trafficking molecule for multi‐subunits transmembrane GABAARs.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.