A Genetic Screen to Uncover Mechanisms Underlying Lipid Transfer Protein Function at Membrane Contact Sites

Overview

Journal Life Sci Alliance

Specialties Biochemistry
Biology
Cell Biology
Molecular Biology

Date 2024 Mar 18

PMID 38499328

Authors

Shirish Mishra

Vaishnavi Manohar

Shabnam Chandel

Tejaswini Manoj

Subhodeep Bhattacharya

Nidhi Hegde

Vaisaly R Nath

Harini Krishnan

Corinne Wendling

Thomas Di Mattia

Arthur Martinet

Prasanth Chimata

Fabien Alpy

Padinjat Raghu

Affiliations

Soon will be listed here.

Abstract

Lipid transfer proteins mediate the transfer of lipids between organelle membranes, and the loss of function of these proteins has been linked to neurodegeneration. However, the mechanism by which loss of lipid transfer activity leads to neurodegeneration is not understood. In photoreceptors, depletion of retinal degeneration B (RDGB), a phosphatidylinositol transfer protein, leads to defective phototransduction and retinal degeneration, but the mechanism by which loss of this activity leads to retinal degeneration is not understood. RDGB is localized to membrane contact sites through the interaction of its FFAT motif with the ER integral protein VAP. To identify regulators of RDGB function in vivo, we depleted more than 300 VAP-interacting proteins and identified a set of 52 suppressors of The molecular identity of these suppressors indicates a role of novel lipids in regulating RDGB function and of transcriptional and ubiquitination processes in mediating retinal degeneration in The human homologs of several of these molecules have been implicated in neurodevelopmental diseases underscoring the importance of VAP-mediated processes in these disorders.

Citing Articles

Editorial on Special Collection in : Lipid Transfer Proteins: From Molecular Mechanisms to Functional Validation.

Mesmin B Contact (Thousand Oaks). 2025; 8:25152564251322628.

PMID: 39991262 PMC: 11843700. DOI: 10.1177/25152564251322628.

Mammalian START-like phosphatidylinositol transfer proteins - Physiological perspectives and roles in cancer biology.

Pathak A, Willis K, Bankaitis V, McDermott M Biochim Biophys Acta Mol Cell Biol Lipids. 2024; 1869(7):159529.

PMID: 38945251 PMC: 11533902. DOI: 10.1016/j.bbalip.2024.159529.

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