ALIX

ALIX (PDCD6IP / programmed cell death 6 interacting protein)

一行要約

ESCRT 機構と協働する accessory scaffold protein。N 末端 Bro1 ドメインで ESCRT-III サブユニット (CHMP4) を直接リクルートし、中央 V ドメインで cargo (syntenin など) を結合、C 末端 PRR (proline-rich region) で TSG101 や CIN85 と相互作用する三領域構造を持つ。Baietti らはエクソソーム biogenesis において syndecan – Syntenin – ALIX 経路が ESCRT-I (TSG101) 非依存的に ILV 形成を駆動する parallel route を確立し (Nat Cell Biol 2012)、ALIX を canonical ESCRT-dependent / -independent biogenesis の蝶番因子として位置づけた。

主要エビデンス

Syndecan-syntenin-ALIX route: heparan sulfate proteoglycan である syndecan の cytoplasmic tail に Syntenin PDZ ドメインが結合し、syntenin LYPx motif が ALIX V ドメインと相互作用。ALIX が ESCRT-III (CHMP4) をリクルートして ILV 形成を完了する。この経路は TSG101 / ESCRT-I 非依存的。

ウイルス budding: HIV-1 / EIAV など多くのレトロウイルスで p6 / p9 Gag の YPx_nL motif が ALIX V ドメインに結合し、retrovirus budding を仲介する。

細胞分裂 (cytokinesis): ALIX は midbody 形成において ESCRT-III をリクルートする因子としても重要。

メカニズム

Bro1 ドメイン: CHMP4 (ESCRT-III) と直接結合し、membrane scission machinery をリクルート。

V ドメイン: cargo / adaptor recognition。Syntenin の LYPxL / LYPxnL motif (YPxL motif family) を結合し、syndecan-derived heparan sulfate cluster を ILV 内へ取り込む。

PRR (proline-rich region): TSG101 と相互作用してESCRT-I 経路にも cross-talk、CIN85 との結合は cargo trafficking を modulate する。

膜物理学: ALIX 単独では in vitro で negative-curvature 膜変形を induce、ESCRT-III の触媒作用と併せて inward budding-scission を完遂する。

関連エンティティ・概念

• Syndecan-syntenin-ALIX route: Syntenin — 直接の上流 partner
• ESCRT machinery: TSG101 — parallel canonical route
• Tetraspanin EV markers: CD9 / CD63 / CD81
• Trafficking: Rab27
• Pathway: Exosome-biogenesis-pathway
• Concept: EV-mediated-intercellular-communication / EV-organotropism / Exosomal-PD-L1
• MOC: cancer-extracellular-vesicles

関連論文

直近 30 件のみ表示中 (関連 120 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Extracellular vesicles

• Liu et al. ACSApplMaterInterfaces 2024 — Cell-specific impacts of surface coating composition on extracellular vesicle secretion
• Schmidt et al. AmJPhysiolCellPhysiol 2026 — Extracellular vesicles in exhaled breath condensate as emerging biomarkers in lung cancer
• Clancy et al. AnnuRevPathol 2023 — Tumor-derived extracellular vesicles multifunctional entities in the tumor microenvironment
• Tang et al. BrainRes 2023 — Activated neutrophil-derived exosomes contribute to blood-brain barrier damage and hemorrhagic transformation after
• Kalluri et al. Cell 2023 — The role of extracellular vesicles in cancer
• Tsering et al. CellDeathDis 2024 — Extracellular vesicle-associated DNA ten years since its discovery in human blood
• Tang et al. CellSignal 2025 — N2 neutrophils induce cell stemness reprogramming to promote gastric cancer progression via exosomal miRNAs
• Moon et al. Cells 2022 — Exosome as a delivery vehicle for cancer therapy
• Lucotti et al. EMBOJ 2022 — Extracellular vesicles and particles impact the systemic landscape of cancer
• Cocozza et al. EMBOJ 2023 — Extracellular vesicles and co-isolated endogenous retroviruses from murine cancer cells differentially affect dendritic
• Ramos et al. FluidsBarriersCNS 2022 — Zaldivar-Extracellular vesicles through the blood-brain barrier a review
• Leary et al. JExtracellVesicles 2022 — Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes
• Liu et al. JExtracellVesicles 2022 — Extracellular vesicles from lung tissue drive bone marrow neutrophil recruitment in inflammation
• Yates et al. JExtracellVesicles 2022 — In sickness and in health the functional role of extracellular vesicles in physiology and pathology in vivo part I
• Blavier et al. JExtracellVesicles 2023 — The capture of extracellular vesicles endogenously released by xenotransplanted tumours induces an inflammatory
• Crescitelli et al. JExtracellVesicles 2025 — Recommendations for studying in situ extracellular vesicles from solid tissue
• De et al. JExtracellVesicles 2026 — Characterizing the fate of anti-CS1 nanobody displaying extracellular vesicles in multiple myeloma
• Han et al. MolCancer 2022 — Exosome biogenesis machinery, regulation, and therapeutic implications in cancer
• Radler et al. MolTher 2023 — Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading
• Tian et al. NatBiomedEng 2026 — Skeletal-muscle-targeted non-viral delivery of full-length DMD mRNA for duchenne muscular dystrophy
• Arya et al. NatCellBiol 2022 — Ceramide-rich microdomains facilitate nuclear envelope budding for non-conventional exosome formation
• Palmulli et al. NatCellBiol 2024 — CD63 sorts cholesterol into endosomes for storage and distribution via exosomes
• Goh et al. NatCommun 2026 — Sarcopenia promotes tumorigenesis by disrupting NOTCH-SDC2-regulated biogenesis of muscle-derived extracellular vesicles
• Shen et al. NatCommun 2026 — Co-enrichment of proteins in extracellular vesicles
• Dixson et al. NatRevMolCellBiol 2023 — Context-specific regulation of extracellular vesicle biogenesis and cargo selection
• Ma et al. SciTranslMed 2025 — Tumor extracellular vesicle-derived PD-L1 promotes T cell senescence through lipid metabolism reprogramming

Basic-Liquid-biopsy

• Ring et al. NatRevCancer 2023 — Biology, vulnerabilities and clinical applications of circulating tumour cells

Basic-Neutrophil and myeloid cell

• Hsu et al. Cell 2025 — Neutrophil-derived vesicles control complement activation to facilitate inflammation resolution
• Chen et al. FrontImmunol 2022 — Roles of the exosomes derived from myeloid-derived suppressor cells in tumor immunity and cancer progression

Clinical-SCLC

• Redin et al. JThoracOncol 2022 — YES1 is a druggable oncogenic target in SCLC