Membrane traffic in the late endocytic pathway

晚期内吞途径中的膜运输

• 批准号: MR/M010007/1
• 负责人: Paul Luzio
• 金额: $ 85.03万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM010007%2F1
• 关键词: Membrane; traffic; late; endocytic; pathway

Cells are compartmentalized by specialized organelles (little organs within each cell), and cargo including proteins is moved between these compartments by the trafficking of vesicles (little bubbles surrounded by a thin membrane made of a fatty substance called phospholipid and studded with proteins). Some of the cargo is taken up into the cells by vesicles formed at the cell surface that deliver their cargo to organelles called endosomes, endolysosomes and lysosomes. Lysosomes act as storage organelles for enzymes that degrade cargo that is delivered from the cell surface or other parts of the cell. Degradation occurs in endolysosomes formed by the fusion of endosomes with lysosomes. We aim to understand the endolysosome better as the compartment in which degradation takes place. We also aim to understand the proteins that make up the machinery necessary to regulate, coordinate and achieve membrane fusion between endosomes and lysosomes. There are many diseases in which defects in the cell surface and/or in membrane traffic to lysosomes occur. These include rare genetic diseases such as the lysosomal storage disorders and more common diseases including diabetes, atherosclerosis and neurodegenerative diseases as well as infectious diseases where microbes subvert the membrane traffic system in order to infect cells. In the long term our work will contribute to developing better ways of targeting drugs to particular sites within cells for more specific drug therapies.

细胞由专门的细胞器（每个细胞内的小器官）划分，包括蛋白质在内的货物通过囊泡（被称为磷脂的脂肪物质制成的薄膜包围的小气泡，并布满蛋白质）的运输在这些区室之间移动。一些货物被细胞表面形成的囊泡吸收到细胞中，这些囊泡将货物递送到称为内体、内溶酶体和溶酶体的细胞器中。溶酶体充当酶的储存细胞器，降解从细胞表面或细胞其他部分传递的物质。降解发生在由内体与溶酶体融合形成的内溶酶体中。我们的目标是更好地了解内溶酶体作为发生降解的隔室。我们还旨在了解构成调节、协调和实现内体和溶酶体之间膜融合所需机制的蛋白质。许多疾病都会出现细胞表面和/或溶酶体膜运输的缺陷。其中包括罕见的遗传疾病，如溶酶体贮积症和更常见的疾病，包括糖尿病、动脉粥样硬化和神经退行性疾病，以及微生物破坏膜运输系统以感染细胞的传染病。从长远来看，我们的工作将有助于开发更好的方法，将药物靶向细胞内的特定位点，以实现更具体的药物治疗。

项目成果

A dysfunctional endolysosomal pathway common to two sub-types of demyelinating Charcot-Marie-Tooth disease.

• DOI: 10.1186/s40478-020-01043-z
• 发表时间: 2020-10-15
• 期刊: Acta neuropathologica communications
• 影响因子: 7.1
• 作者: Edgar JR;Ho AK;Laurá M;Horvath R;Reilly MM;Luzio JP;Roberts RC
• 通讯作者: Roberts RC

Endolysosomes Are the Principal Intracellular Sites of Acid Hydrolase Activity.

• DOI: 10.1016/j.cub.2016.06.046
• 发表时间: 2016-09-12
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Bright, Nicholas A.;Davis, Luther J.;Luzio, J. Paul
• 通讯作者: Luzio, J. Paul

A non-canonical ESCRT pathway, including histidine domain phosphotyrosine phosphatase (HD-PTP), is used for down-regulation of virally ubiquitinated MHC class I.

• DOI: 10.1042/bj20150336
• 发表时间: 2015-10-01
• 期刊: The Biochemical journal
• 作者: Parkinson MD;Piper SC;Bright NA;Evans JL;Boname JM;Bowers K;Lehner PJ;Luzio JP
• 通讯作者: Luzio JP

Organelle tethering, pore formation and SNARE compensation in the late endocytic pathway.

• DOI: 10.1242/jcs.255463
• 发表时间: 2021-05-15
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Davis LJ;Bright NA;Edgar JR;Parkinson MDJ;Wartosch L;Mantell J;Peden AA;Luzio JP
• 通讯作者: Luzio JP

CALM regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature.

• DOI: 10.1016/j.devcel.2015.03.002
• 发表时间: 2015-04-20
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: Miller, Sharon E.;Mathiasen, Signe;Bright, Nicholas A.;Pierre, Fabienne;Kelly, Bernard T.;Kladt, Nikolay;Schauss, Astrid;Merrifield, Christien J.;Stamou, Dimitrios;Hoening, Stefan;Owen, David J.
• 通讯作者: Owen, David J.