RabGEFs are a major determinant for specific Rab membrane targeting
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RabGEFs are a major determinant for specific Rab membrane targeting. / Blümer, Julia; Rey, Juliana; Dehmelt, Leif; Mazel, Tomáš; Wu, Yao-Wen; Bastiaens, Philippe; Goody, Roger S; Itzen, Aymelt.
in: J CELL BIOL, Jahrgang 200, Nr. 3, 04.02.2013, S. 287-300.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - RabGEFs are a major determinant for specific Rab membrane targeting
AU - Blümer, Julia
AU - Rey, Juliana
AU - Dehmelt, Leif
AU - Mazel, Tomáš
AU - Wu, Yao-Wen
AU - Bastiaens, Philippe
AU - Goody, Roger S
AU - Itzen, Aymelt
PY - 2013/2/4
Y1 - 2013/2/4
N2 - Eukaryotic cells critically depend on the correct regulation of intracellular vesicular trafficking to transport biological material. The Rab subfamily of small guanosine triphosphatases controls these processes by acting as a molecular on/off switch. To fulfill their function, active Rab proteins need to localize to intracellular membranes via posttranslationally attached geranylgeranyl lipids. Each member of the manifold Rab family localizes specifically to a distinct membrane, but it is unclear how this specific membrane recruitment is achieved. Here, we demonstrate that Rab-activating guanosine diphosphate/guanosine triphosphate exchange factors (GEFs) display the minimal targeting machinery for recruiting Rabs from the cytosol to the correct membrane using the Rab-GEF pairs Rab5A-Rabex-5, Rab1A-DrrA, and Rab8-Rabin8 as model systems. Specific mistargeting of Rabex-5/DrrA/Rabin8 to mitochondria led to catalytic recruitment of Rab5A/Rab1A/Rab8A in a time-dependent manner that required the catalytic activity of the GEF. Therefore, RabGEFs are major determinants for specific Rab membrane targeting.
AB - Eukaryotic cells critically depend on the correct regulation of intracellular vesicular trafficking to transport biological material. The Rab subfamily of small guanosine triphosphatases controls these processes by acting as a molecular on/off switch. To fulfill their function, active Rab proteins need to localize to intracellular membranes via posttranslationally attached geranylgeranyl lipids. Each member of the manifold Rab family localizes specifically to a distinct membrane, but it is unclear how this specific membrane recruitment is achieved. Here, we demonstrate that Rab-activating guanosine diphosphate/guanosine triphosphate exchange factors (GEFs) display the minimal targeting machinery for recruiting Rabs from the cytosol to the correct membrane using the Rab-GEF pairs Rab5A-Rabex-5, Rab1A-DrrA, and Rab8-Rabin8 as model systems. Specific mistargeting of Rabex-5/DrrA/Rabin8 to mitochondria led to catalytic recruitment of Rab5A/Rab1A/Rab8A in a time-dependent manner that required the catalytic activity of the GEF. Therefore, RabGEFs are major determinants for specific Rab membrane targeting.
KW - Animals
KW - COS Cells
KW - Cell Membrane
KW - Cercopithecus aethiops
KW - Guanine Nucleotide Exchange Factors
KW - Humans
KW - Microscopy, Confocal
KW - Mitochondria
KW - Mitochondrial Membranes
KW - Models, Biological
KW - Mutant Proteins
KW - Protein Structure, Tertiary
KW - Protein Transport
KW - Subcellular Fractions
KW - rab GTP-Binding Proteins
KW - rab5 GTP-Binding Proteins
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1083/jcb.201209113
DO - 10.1083/jcb.201209113
M3 - SCORING: Journal article
C2 - 23382462
VL - 200
SP - 287
EP - 300
JO - J CELL BIOL
JF - J CELL BIOL
SN - 0021-9525
IS - 3
ER -