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Intracellular Compartmentation

Group Leader:



icrea
1990-1995 Assistant Professor, UC San Diego, Biology Department.
1995-1999 Associate Professor (tenured), UC San Diego, Biology Department.
1999-2007 Professor, UC San Diego, Cell and Developmental Biology Department.
1998-2003 Member, Mario Negri Sud Research Institute, Italy.
1999-2000 ICREA Visiting scientist, University of Barcelona, Spain.
2007 ICREA Research Professor and Group Leader at the CRG, Barcelona, Spain / Coordinator of the Cell & Developmental Biology Programme, CRG, Barcelona, Spain

Summary
Our aim is to understand the mechanism of transport carrier formation from the Golgi and the process by which Golgi membranes are partitioned into daughter cells during cell division. Our findings have revealed the involvement of a signaling cascade that regulates the fission of cargo filled transport carriers of the Golgi to cell surface pathway. This involves a trimeric G-protein mediated event that leads to the recruitment and activation of a serine/threonine kinase PKD to Golgi membranes. PKD has a number of substrates on the Golgi membranes and our working hypothesis is that PKD, through its partners, generates a local pool of diacylglycerol (DAG). This reaction is ultimately used to regulate fission thus liberating cargo filled transport carriers from the Golgi membranes. The PKD dependent Golgi vesiculation is being reconstituted in vitro to test the significance of modified lipids in membrane fission.

A genome wide screen has revealed a number of new transport components, which we call TANGO for Transport And Golgi Organization. These components are being characterized for their specific roles in protein secretion.

A genome wide screen was carried out to identify components involved in secretion of Mucin. Uncontrolled secretion of Mucin is one of the main causes of Asthma. Our aim is to understand how secretion of Mucin is regulated and to identify chemicals that specifically affect Mucin secretion by binding to the components identified in our screen.

We have recently found that a Golgi associated protein called GRASP is required for the secretion of proteins lacking a conventional signal sequence. This family of proteins includes interleukins, Galectins, FGF and MIF. We are using in vitro approaches and mouse models to understand the mechanism and physiological significance of this unconventional (meaning without entering the ER-Golgi pathway) mode of secretion.     

Golgi membranes undergo extensive fragmentation during mitosis in mammalian cells. We have found that this fragmentation begins early in G2, which if blocked, prevents the entry of cells into mitosis. Our aim is to understand the molecular mechanism of this Golgi organization specific cell cycle checkpoint.  An understanding of coordination of the Golgi specific cell cycle checkpoints with other checkpoints (DNA damage, Spindle dynamics) is key to the overall understanding of the mechanisms regulating cell division.

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Research Lines
Biogenesis of Golgi to cell surface transport carriers
Molecular understanding of the pathology of Asthma: Mechanism of mucin secretion
Unconventional protein secretion
Mechanism of Golgi biogenesis
Identification of a Golgi organization specific cell cycle check point
Selected Publications

von Blume J, Alleaume AM, Kienzle C, Carreras-Sureda A, Valverde M, Malhotra V..
Cab45 is required for Ca2+-dependent secretory cargo sorting at the trans-Golgi network
Journal of Cell Biology 199(7):1057-66. doi: 10.1083/jcb.201207180 (2012). abstract
Duran JM, Campelo F, van Galen J, Sachsenheimer T, Sot J, Egorov MV, Rentero C, Enrich C, Polishchuk RS, Goñi FM, Brügger B, Wieland F, Malhotra V..
Sphingomyelin organization is required for vesicle biogenesis at the Golgi complex
EMBO Journal 31(24):4535-46. doi: 10.1038/emboj.2012.317 (2012). abstract
Wakana Y, van Galen J, Meissner F, Scarpa M, Polishchuk RS, Mann M, Malhotra V..
A new class of carriers that transport selective cargo from the trans Golgi network to the cell surface
EMBO Journal doi: 10.1038/emboj.2012.235. [Epub ahead of print] (2012). abstract
Curwin AJ, von Blume J, Malhotra V..
Cofilin mediated sorting and export of specific cargo from the Golgi apparatus in yeast
Molecular Biology of the Cell 23(12):2327-38. doi: 10.1091/mbc.E11-09-0826 (2012).
Bruns C, McCaffery JM, Curwin AJ, Duran JM, Malhotra V..
Biogenesis of a novel compartment for autophagosome-mediated unconventional protein secretion
Journal of Cell Biology 195(6):979-92. Epub 2011 Dec 5 (2011). abstract

 
 
 

Group Members

 
Campelo, Felix
Cruz, David
Curwin, Amy
Duran, Juan Manuel
Erlmann, Patrik
Mitrovic, Sandra
Nogueira, Cristina
Ortega, María
Popoff, Jean-François
Scarpa, Margherita
Villeneuve, Julien