TENT5/FAM46: An Enigmatic Family of Secretory Tuners.

IF 3.6 3区生物学 Q3 CELL BIOLOGY

Traffic Pub Date : 2025-04-01 DOI:10.1111/tra.70011

Daniel Lacidogna, Sara Pennacchio, Enrico Milan

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引用次数: 0

Abstract

Human TENT5 family comprises four members (A-D) associated with different diseases of secretory cells. Homozygous mutations in TENT5A cause a rare form of osteogenesis imperfecta due to impaired collagen deposition by osteoblasts. TENT5C is frequently mutated or deleted in patients with multiple myeloma, the cancer of antibody-secreting plasma cells, and TENT5D alterations result in male infertility. TENT5 members are noncanonical poly(A)polymerases that selectively stabilize mRNAs encoding endoplasmic reticulum-imported proteins, thus promoting the expression of secretory cargoes and proteins involved in folding, glycosylation, and trafficking along the secretory apparatus. This specificity has been proposed to be linked to TENT5 localization at the membrane of the endoplasmic reticulum, thanks to their interaction with transmembrane FNDC3 proteins. Recently, key roles of TENT5 proteins have been described in cancer, bone homeostasis, immunity, stemness, and fertility. This review will comprehensively analyze the identified cellular functions of this novel family of secretory tuners in physiological and pathological conditions, highlighting the proposed molecular mechanisms and the remaining open questions.

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一个神秘的秘书特纳家族。

人类TENT5家族包括4个成员（A-D），与不同的分泌细胞疾病相关。由于成骨细胞的胶原沉积受损，TENT5A的纯合突变导致一种罕见的成骨不完全性。在多发性骨髓瘤（抗体分泌浆细胞癌）患者中，TENT5C经常发生突变或缺失，而TENT5D的改变会导致男性不育。TENT5成员是非规范聚(A)聚合酶，可选择性地稳定编码内质网进口蛋白的mrna，从而促进分泌货物和参与折叠、糖基化和沿分泌装置运输的蛋白质的表达。这种特异性被认为与TENT5在内质网膜上的定位有关，这要归功于它们与跨膜FNDC3蛋白的相互作用。最近，TENT5蛋白在癌症、骨稳态、免疫、干细胞和生育方面的关键作用被描述。本文将全面分析这一新型分泌调谐器家族在生理和病理条件下的细胞功能，重点介绍其分子机制和尚未解决的问题。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Traffic 生物-细胞生物学

CiteScore

8.10

自引率

2.20%

发文量

审稿时长

2 months

期刊介绍： Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.