Molecular Physiology of the Cell

Study on membrane microdomains protecting transporters from ubiquitylation and endocytosis published in PNAS

The plasma membrane of cells is known to be compartmentalized into domains enriched in specific lipids and proteins. The best studied membrane domains found in yeast is the “Eisosome Membrane Compartment” (EMC) accumulating diverse proteins including several nutrient transporters. However, how and why these transporters preferentially partition in these EMCs remains unknown.

In a novel study published in PNAS and mainly conducted by Christos Gournas (FNRS postdoc), we report that segregation of the Can1 arginine transporter into EMCs is dictated by its conformation and requires proper biogenesis of sphingolipids. Furthermore, this clustering confers to Can1 and other transporters protection from ubiquitin-dependent endocytosis. This protective role is particularly pronounced under nutrient starvation conditions, where EMCs increase in size and number. It allows cells to preserve a fraction of their nutrient transporters from bulk endocytosis occuring in parallel with autophagy, and to more efficiently resume growth when replenishing compounds are available. This work reveals nutrient-regulated protection from endocytosis as an important role for protein partitioning into membrane domains. It also suggests that EMC-like microdomains existing in human cells could ensure a similar function. This study was supported by the FNRS and conducted in collaboration with the Centre for Microscopy and Molecular Imaging (CMMI) of the Biopark and with Dr. D. Tyteca (UCL, De Duve Institute).

Article : Conformation-dependent partitioning of yeast nutrient transporters into starvation-protective membrane domains. Gournas C, Gkionis S, Carquin M, Twyffels L, Tyteca D, André B. PNAS (in press).

“Cystinosis Research Foundation” 2018 symposium

Bruno André attended to the last scientific symposium organized by the “Cystinosis Research Foundation” (Irvine, USA, March 1-2). The meeting gathered all the research groups supported by the CRF and conducting fundamental or clinical research studies on cystinosis, a rare genetic disease caused by mutations in the CTNS gene. This gene encodes a transporter present at the lysosomal membrane and catalyzing export to the cytosol of cystine, the compound made of two cysteines linked by a disulfide bridge. B. André presented the work carried out in his lab about cysteine transport across the vacuolar membrane in yeast cells.

Elie Saliba received his PhD diploma

On December 20th, Elie Saliba publicly presented his PhD work dealing with a novel mechanism of activation of the TORC1 kinase complex in yeast. He has successfully received his PhD diploma. A great moment for Elie, who was surrounded by his wife, colleagues, and friends. Elie will stay in the lab for a postdoc where he will pursue his work about the role of H+ ATPases in activation of TORC1. Thanks a lot to him for his key contribution to this novel research topic of the lab.

Georgios Kapetanakis obtained a FRIA fellowship

Georgios Kapetanakis was informed by the FNRS that he’s among the laureates of the 2017 competition for FRIA fellowships. Georgios obtained his master diploma last year in the University of Athens (Greece). He did a master thesis work in the lab of Pr. G. Diallinas where he investigated the role of membrane transporters in resistance to specific drugs by the fungus Aspergillus nidulans. During his PhD, Georgios Kapetanakis will investigate the molecular mechanisms of the still-poorly understood phenomenon of amino acid excretion by yeast, in the context of a collaboration with Dr. Isabelle Georis of the IRMW institute (Anderlecht).

ASCB 2017 meeting in Philadelphia

B André attended the annual meeting of the American Society of Cell Biology (ASCB) in Philadelphia (2-6 December). The EMBO was a coorganizer of this major annual cell biology meeting.

Charlotte Felten hired by the lab as technician

We are pleased to announce that the lab has hired Charlotte FELTEN as a new technician. Charlotte obtained her diploma in 2017 at the “Haute Ecole de Louvain en Hainaut” (Fleurus). She did an internship in the Immunobiology group of our institute. Charlotte now joined the lab thanks to a new four-year grant from the Wallonie Region.

Study on FTY720 anticancer drug provoking endocytosis of amino acid transporters in yeast and human cells published in Scientific Reports

FTY720 is a drug causing death of several types of tumour cells. This effect is largely due to its ability to provoke endocytosis of several nutrient transporters. FTY720 also promotes endocytosis of amino acid permeases in yeast. In a study now published in Scientific Reports, Céline Barthelemy and coll. report that FTY720 inhibits the intrinsic activity of transporters, in both yeast and human cells. This is coupled to rapid inhibition of the TORC1 kinase complex, in turn promoting endocytosis of the inactivated transporters. This study sheds new light on how FTY720 kills cancer cells.

“Endocytic trafficking and signaling in health and disease” meeting

Céline Barthelemy attended the EMBO conference presenting the last research progress about “Endocytic trafficking and signaling in health and disease” that was held in Serock, Poland (10-15 September). Céline presented in a poster her last results about the mechanisms through which the anticancer drug FTY720 provokes endocytosis of amino acid transporters in yeast and human cells.

Yeast Genetics and Molecular Biology meeting (Prague, August 2017)

Melody Cools, Elie Saliba and Bruno André have attended the last Yeast Genetics and Molecular Biology meeting that took place in Prague (Czech Republic) between August 27 and September 1. The opening lecture was given by Pr. Yoshinori Ohsumi (Nobel Prize in Physiology or Medicine 2016) about the “Molecular mechanism and physiological role of autophagy”. Melody and Elie were invited to give oral presentations in workshops organized during the meeting. The conference was a great opportunity to learn many novel things, and share and discuss data with colleagues.

Elucitated mechanism of Can1 transporter ubiquitylation published in MBoC

Our last paper entitled “Transition of yeast Can1 transporter to the inward-facing state unveils an alpha-arrestin target sequence promoting its ubiquitylation and endocytosis” has just been published in the journal Molecular Biology of the Cell (MBoC). This study reports that ubiquitylation and endocytosis of the yeast Can1 transporter are triggered by a substrate-elicited change of its conformation (shift to the inward-facing state) coupled to activation of the TORC1 kinase complex. The experimental work was mainly conducted by Christos Gournas and the data of Can1 structural modeling were generated by Martine Prévost and Maria-Eva Krammer (ULB, Structure and Function of Biological Membranes).