Biology subjects

Ibe, N. U.

Publications and source records attributed to Ibe, N. U..

2 recordsLinked to original sources

bioRxiv2022

A new LD protein, ApoL6 disrupts the Perilipin 1-HSL interaction to inhibit lipolysis

ApoL6 is a new LD-associated protein containing an apoprotein-like domain, expressed mainly in adipose tissue, specifically in adipocytes. ApoL6 expression is low in fasting but induced upon feeding. ApoL6 knockdown results in smaller LD with lower triglyceride (TAG) content in adipocytes, while ApoL6 overexpression causes larger LD with higher TAG content. We show that ApoL6 effect in adipocytes is by inhibition of lipolysis. While ApoL6, Perilipin 1 (Plin1) and HSL can form a complex on LD, C-terminal domain of ApoL6 directly interacts with Plin1, to compete with Plin1 binding to HSL through Plin1 N-terminal domain, thereby keeping HSL in a "stand by" status. Thus, ApoL6 ablation decreases WAT mass, protecting mice from diet-induced obesity, while adipose overexpression increases WAT mass to bring obesity and insulin resistance with hepatosteatosis, making ApoL6 a potential future target against obesity and diabetes.

molecular biology↗

bioRxiv2020

Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors

The intracellular bacterial pathogen Legionella pneumophila (L.p.) secretes ~330 effector proteins into the host cell to sculpt an Endoplasmic Reticulum (ER)-derived replicative niche. We previously reported five L.p. effectors that inhibit IRE1, a key sensor of the homeostatic unfolded protein response (UPR) pathway. In this study, we discovered a subset of L.p. toxins that selectively activate the UPR sensor ATF6, resulting in its cleavage, nuclear translocation and target gene transcription without affecting other UPR sensors such as PERK. In a deviation from the conventional model, this L.p. dependent activation of ATF6 does not require its transport to the Golgi or its cleavage by the S1P/S2P proteases. We believe that our findings highlight the unique regulatory control that L.p. exerts upon the three UPR sensors and expand the repertoire of bacterial proteins that selectively perturb host homeostatic pathways.

cell biology↗