TY - JOUR
T1 - A plasma-membrane E-MAP reveals links of the eisosome with sphingolipid metabolism and endosomal trafficking
AU - Aguilar, Pablo S.
AU - Fröhlich, Florian
AU - Rehman, Michael
AU - Shales, Mike
AU - Ulitsky, Igor
AU - Olivera-Couto, Agustina
AU - Braberg, Hannes
AU - Shamir, Ron
AU - Walter, Peter
AU - Mann, Matthias
AU - Ejsing, Christer S.
AU - Krogan, Nevan J.
AU - Walther, Tobias C.
N1 - Funding Information:
We thank members of the Walther and Krogan laboratory for critical reading and comments, J. Brickner for suggestions, Ulrike Laabs for excellent technical assistance, O. Nørregaard Jensen (University of Southern Denmark) for providing access to the Nanomate Triversa used for the lipidomic experiments and P. Kemmeren for establishing the database. This work was supported by the Max Planck Society (T.C.W.), the German Research Foundation (DFG; T.C.W.), the German-Israeli Foundation (T.C.W.), the US National Institutes of Health, the Searle, Sandler and Keck Foundations (N.J.K.), the International Human Frontier Science Program (HFSP; T.C.W.), the Israel Science Foundation (grant no. 802/08; R.S.), the Edmond J. Safra Bioinformatics program at Tel Aviv University (I.U.), the Programa de Apoyo Sectorial a la Estrategia Nacional de Innovación (INNOVA URUGUAY, DCI-ALA/2007/19.040, P.S.A.), the Agencia Nacional de Investigación e Innovación (ANII, A.O.-C.), the Danish Council for Independent Research (DOK1155860, C.S.E.) and Lundbeckfonden (R45-A4342, C.S.E.).
PY - 2010/7
Y1 - 2010/7
N2 - The plasma membrane delimits the cell and controls material and information exchange between itself and the environment. How different plasma-membrane processes are coordinated and how the relative abundance of plasma-membrane lipids and proteins is homeostatically maintained are not yet understood. Here, we used a quantitative genetic interaction map, or E-MAP, to functionally interrogate a set of 400 genes involved in various aspects of plasma-membrane biology, including endocytosis, signaling, lipid metabolism and eisosome function. From this E-MAP, we derived a set of 57,799 individual interactions between genes functioning in these various processes. Using triplet genetic motif analysis, we identified a new component of the eisosome, Eis1, and linked the poorly characterized gene EMP70 to endocytic and eisosome function. Finally, we implicated Rom2, a GDP/GTP exchange factor for Rho1 and Rho2, in the regulation of sphingolipid metabolism.
AB - The plasma membrane delimits the cell and controls material and information exchange between itself and the environment. How different plasma-membrane processes are coordinated and how the relative abundance of plasma-membrane lipids and proteins is homeostatically maintained are not yet understood. Here, we used a quantitative genetic interaction map, or E-MAP, to functionally interrogate a set of 400 genes involved in various aspects of plasma-membrane biology, including endocytosis, signaling, lipid metabolism and eisosome function. From this E-MAP, we derived a set of 57,799 individual interactions between genes functioning in these various processes. Using triplet genetic motif analysis, we identified a new component of the eisosome, Eis1, and linked the poorly characterized gene EMP70 to endocytic and eisosome function. Finally, we implicated Rom2, a GDP/GTP exchange factor for Rho1 and Rho2, in the regulation of sphingolipid metabolism.
UR - http://www.scopus.com/inward/record.url?scp=77954385031&partnerID=8YFLogxK
U2 - 10.1038/nsmb.1829
DO - 10.1038/nsmb.1829
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AN - SCOPUS:77954385031
VL - 17
SP - 901
EP - 908
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 7
ER -