
Ezrin은 EGFR-AKT 신호 전달 경로에서 TSC 복합체의 활성화를 조절하는 핵심 단백질입니다.


coremsg

Endosomes have emerged as major signaling hubs where different internalized ligand-receptor complexes are integrated and the outcome of signaling pathways are organized to regulate the strength and specificity of signal transduction events. Ezrin, a major membrane-actin linker that assembles and coordinates macromolecular signaling complexes at membranes, has emerged recently as an important regulator of lysosomal function. Here, we report that endosomal-localized EGFR/Ezrin complex interacts with and triggers the inhibition of the Tuberous Sclerosis Complex (TSC) in response to EGF stimuli. This is regulated through activation of the AKT signaling pathway. Loss of Ezrin was deficient in TSC repression by EGF and culminated in translocation of TSC to lysosomes triggering suppression of mTORC1 signaling. Overexpression of constitutively active EZRINT567D is sufficient to relocalize TSC to the endosomes and reactivate mTORC1. Our findings identify EZRIN as a critical regulator of autophagy via TSC in response to EGF stimuli and establish the central role of early endosomal signaling in the regulation of mTORC1. Consistently, Medaka fish deficient for Ezrin exhibit defective endo-lysosomal pathway, attributable to the compromised EGFR/AKT signaling, ultimately leading to retinal degeneration. Our data identify a pivotal mechanism of endo-lysosomal signaling involving Ezrin and its associated EGFR/TSC complex, which are essential for retinal function.

### Competing Interest Statement

The authors have declared no competing interest.

*   ### Abbreviations
    
    RPE
    :   retinal pigment epithelium
    POS
    :   photoreceptor outer segment
    ERM
    :   Ezrin-radix-moesin
    EZR
    :   Ezrin
    NHE1
    :   sodium-hydrogen antiporter 1
    EGFR
    :   epidermal growth factor receptor
    Vsp11
    :   vacuolar protein sorting 11
    PI3K
    :   Phosphoinositide-3-kinase
    AKT
    :   protein kinase B
    EGF
    :   epidermal growth factor
    TSC
    :   Tuberous sclerosis proteins
    mTOR
    :   mammalian target of rapamycin
    GTPase
    :   Guanine nucleotide-binding proteins
    MEF
    :   Mouse Primary Embryonic Fibroblasts
    LAMP1
    :   Lysosomal Associated Membrane Protein 1
    LC3
    :   Microtubule-associated proteins 1A/1B light chain 3B
    CTSB
    :   Cathepsin B
    HER3
    :   human epidermal growth factor receptor 3
    HER2
    :   human epidermal growth factor receptor 2
    EEA1
    :   early endosome antigen 1
    MAPK
    :   mitogen-activated protein kinase
    MK2
    :   Mitogen-activated protein kinase-activated protein kinase 2
    ARPE
    :   Retinal Pigment Epithelial Cells.

Ezrin defines TSC1 activation at endosomal compartments through EGFR-AKT signaling

egfr-신호-전달-경로에서-ezrin이-tsc1-활성화를-정의합니다


EGFR 신호 전달 경로에서 Ezrin이 TSC1 활성화를 정의합니다
