Molecular mechanisms of endolysosomal homeostasis and extracellular vesicles. PI: Albert Lu Lopez

Presentation

 
The Endolysosomal compartment plays a central role in metabolic and signaling regulation in cells. In addition, this membrane-bound compartment is the cellular location where exosomes are generated, which are released upon endolysosomal exocytosis.
Our research group seeks to understand the molecular mechanisms that regulate different aspects of endolysosomal homeostasis and the biology of extracellular vesicles (EVs), including exosomes. We have previously developed CRISPR/Cas9 genetic screening approaches to identify genes involved in the regulation of the underlying biology of EVs and endolysosomal lipid trafficking. Our laboratory uses biochemical, cell biological and genetics approaches, including functional genomics screens, to investigate exosomal cargo sorting and lipid trafficking pathways from endolysosomes in different disease contexts.
 
KEYWORDS: Endolysosomes, Exosomes, Extracellular vesicles, EV-mediated communication, KRAS signaling, cholesterol, membrane trafficking

Albert Lu Lopez
Lecturer professor
albertlu@ub.edu

 

Moisés Castellà Giner
Postoctoral researcher
moises.castella@ub.edu

 

Marta Esplugas Miravent
Undergraduate student
martaesplum@gmail.com

Elsa Meneses-Salas
Postoctoral researcher
elsameneses@ub.edu

 

Pol Sauqué i Martínez
PhD student
psauquma7@alumnes.ub.edu

Elucidating the molecular mechanisms of microRNA sorting into exosomes in colon cancer cells.

Unraveling the role of  SNX13 in endolysosomal cholesterol transport in the context of Niemann-Pick disease type C.

Dissecting exosome-mediated bis(monocylglycero)phosphate release in LRRK2-associated Parkinson's disease.

Role of KRAS and its phosphorylation in the epithelial organization, invasion and biogenesis of exosomes from colorectal cancer cells (PID2022-138728OB-I00)

Funding Agency: Ministerio de Ciencia e Innovación (Spain)
Period: 01/09/2023-31/08/2026
PI: Albert Lu (PI2, UB) and Neus Agell (PI1, UB)

LRRK2 kinase and glucocerebrosidase (GCase) activity-mediated regulation of a lysosomal phospholipid, bis(monoacylglycerol)-phosphate (BMP)

Funding Agency: The Michael J. Fox Foundation for Parkinson’s Research
Period: 01/12/2023-30/11/2025
PI: Albert Lu (UB)

Role of SNX13 in an NPC1 bypass cholesterol egress pathway

Funding Agency: Ara Parseghian Medical Research Fund
Period: 01/07/2023-30/06/2024
PI: Albert Lu (UB)

LRRK2 kinase and glucocerebrosidase (GCase) activity-mediated regulation of a lysosomal phospholipid, bis(monoacylglycerol)-phosphate (BMP)

Funding Agency: The Michael J. Fox Foundation for Parkinson’s Research
Period: 01/04/2021-31/03/23
PI: Albert Lu (PI2, UB) and Dr.Kalpana Merchant (PI1, Northwestern University, US)

2021 SGR 00284 Cell Compartments:trafficking and signaling in health and disease

Funding Agency: Generalitat de Catalunya
Period: 01/01/2022- 31/12/2024
PI: N. Agell: Research collaborator: Albert Lu; Granted; UB
Amount: 60.000 €

For more information for PI publications click in the link:

Scopus ID: 55245181700
 
 

Meneses-Salas, E.,   Arnold M., Hsieh, F., Enrich, C., Pfeffer, S.R., Merchant, K. and Lu, A*. Exosome-mediated release of bis(monoacylglycerol)phosphate is regulated by LRRK2 and Glucocerebrosidase activity. bioRxiv 2023.07.12 .548710; doi: 10.1101/ 2023.07.12.548710. *corresponding author.

Lu A. Quantitative Analysis of Extracellular Vesicle Release Using Artificial MicroRNAs. Methods Mol Biol. 2023:2668: 191-207. doi: 10.1007/ 978-1-0716-3203-1_14. PMID: 37140798

Enrich C, Lu A, Tebar F, Rentero C, Grewal T. Ca2+ and Annexins - Emerging Players for Sensing and Transferring Cholesterol and Phosphoinositides via Membrane Contact Sites. Adv Exp Med Biol. 2023:1422: 393-438. doi: 10.1007/ 978-3-031-21547-6_15. PMID: 36988890

Lu A. Endolysosomal cholesterol export: More than just NPC1. Bioessays. 2022 Oct; 44(10):e2200111. doi: 10.1002/ bies.202200111. Epub 2022 Aug 7. PMID: 35934896

Enrich C, Lu A, Tebar F, Rentero C, Grewal T. Annexins Bridging the Gap: Novel Roles in Membrane Contact Site Formation. Front Cell Dev Biol. 2022 Jan 6:9: 797949. doi: 10.3389/ fcell.2021.797949. eCollection 2021. PMID: 35071237

Lu A*, Hsieh F, Sharma BR, Vaughn SR, Enrich C, Pfeffer SR. CRISPR screens for lipid regulators reveal a role for ER-bound SNX13 in lysosomal cholesterol export. J Cell Biol. 2022 Feb 7;221(2): e202105060. doi: 10.1083/ jcb.202105060. Epub 2021 Dec 22. *corresponding author. PMID: 34936700

Jose J, Hoque M, Engel J, Beevi SS, Wahba M, Georgieva MI, Murphy KJ, Hughes WE, Cochran BJ, Lu A, Tebar F, Hoy AJ, Timpson P, Rye KA, Enrich C, Rentero C, Grewal T. Annexin A6 and NPC1 regulate LDL-inducible cell migration and distribution of focal adhesions. Sci Rep. 2022 Jan 12; 12(1): 596. doi: 10.1038/ s41598-021-04584-y. PMID: 35022465

Saha P, Shumate JL, Caldwell JG, Elghobashi-Meinhardt N, Lu A, Zhang L, Olsson NE, Elias JE, Pfeffer SR. Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins. Elife. 2020 May 15:9: e57089. doi: 10.7554/ eLife.57089. PMID: 32410728

Kumar S, Barouch-Bentov R, Xiao F, Schor S, Pu S, Biquand E, Lu A, Lindenbach BD, Jacob Y, Demeret C, Einav S. MARCH8 Ubiquitinates the Hepatitis C Virus Nonstructural 2 Protein and Mediates Viral Envelopment. Cell Rep. 2019 Feb 12;26(7): 1800-1814.e5. doi: 10.1016/ j.celrep.2019.01.075. PMID: 30759391

Lu A*, Wawro P, Morgens DW, Portela F, Bassik MC, Pfeffer SR. Genome-wide interrogation of extracellular vesicle biology using barcoded miRNAs. Elife. 2018 Dec 17:7: e41460. doi: 10.7554/ eLife.41460. PMID: 30556811

Barouch-Bentov R, Neveu G, Xiao F, Beer M, Bekerman E, Schor S, Campbell J, Boonyaratanakornkit J, Lindenbach B, Lu A, Jacob Y, Einav S. Hepatitis C Virus Proteins Interact with the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery via Ubiquitination To Facilitate Viral Envelopment. mBio. 2016 Nov 1;7(6): e01456-16. doi: 10.1128/ mBio.01456-16. PMID: 27803188

Lu A*, Pfeffer SR. A CULLINary ride across the secretory pathway: more than just secretion. Trends Cell Biol. 2014 Jul;24(7):389-99. doi: 10.1016/j.tcb.2014.02.001. *corresponding author. PMID: 24630736

Gelabert-Baldrich M, Soriano-Castell D, Calvo M, Lu A, Viña-Vilaseca A, Rentero C, Pol A, Grinstein S, Enrich C, Tebar F. Dynamics of KRas on endosomes: involvement of acidic phospholipids in its association. FASEB J. (2014) 28(7): 3023-37. doi: 10.1096/ fj.13-241158. PMID: 24719356

Lu A*, Pfeffer SR. Golgi-associated RhoBTB3 targets cyclin E for ubiquitylation and promotes cell cycle progression. J Cell Biol. 2013 Oct 28;203(2): 233-50. doi: 10.1083/ jcb.201305158. Epub 2013 Oct 21. PMID: 24145166

Lu A, Tebar F, Alvarez-Moya B, López-Alcalá C, Calvo M, Enrich C, Agell N, Nakamura T, Matsuda M, Bachs O. A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes. J Cell Biol. 2009 Mar 23;184(6): 863-79. doi: 10.1083/ jcb.200807186. Epub 2009 Mar 16. PMID: 19289794

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