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DTSTART:20180325T030000
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DTSTART:20181028T020000
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DTSTAMP:20260405T162029Z
UID:5aeaf60d31002419555589@ist.ac.at
DTSTART:20180507T160000
DTEND:20180507T171500
DESCRIPTION:Speaker: Fu Li\nhosted by Carl-Philipp Heisenberg\nAbstract: Ra
 b  GTPases are  key  regulators  of  intracellular  vesicle  transport  in
   eukaryotic  cells. Rab family members (>60   Rabs   in   human) localize
    to   distinct   intracellular compartments   and   regulate   multiple 
   steps   of   vesicular   transport. Intracellular membrane trafficking r
 equires correct and specific localization of Rab GTPases. The hypervariabl
 e C-terminal domain (HVD) of  Rabs is posttranslationally  modified by iso
 prenyl moieties that enable membrane association. To elucidate the functio
 n of the HVD\, we have substituted this region with an unnatural polyethyl
 englycol (PEG) linker by using oxime ligation. Through localization studie
 s and functional analyses of semisynthetic PEGylated Rab1\, Rab5\, Rab7\, 
 and Rab35 proteins\, we demonstrate that the role of the HVD of Rabs in me
 mbrane targeting is more complex than previously understood. In our studie
 s\,  we  reveal  the  mechanism  of  Rab35  plasma  membrane targeting.  W
 e  find  that  Rab35  cycles  between  the  plasma  membrane  and  the  Go
 lgi apparatus via  endocytic  trafficking  and  GDI-mediated  recycling.  
 The  C-terminal polybasic  region (HVD) of  Rab35\,  DENN1A\,  OCRL1  and 
  PRA1  (GDF)  play  an important role in spatial cycling of Rab35\, thereb
 y its plasma membrane localization and  function.  We  show  that  OCRL1  
 mutants  lead  to  disruption  of  Rab35  plasma membrane localization and
  function in neurite outgrowth\, suggesting a link of Rab35 to the Lowe sy
 ndrome. Our findings suggest that Rab membrane targeting is dictated by a 
 complex mechanism involving  GEFs\,  GAPs\,  effectors\,  and  C-terminal 
  interaction  with  membranes  to varying extents\, and possibly other bin
 ding partners.
LOCATION:Meeting room 2nd floor / Bertalanffy Bldg. (I04.2OG - LAB)\, ISTA
ORGANIZER:lalesch@ist.ac.at
SUMMARY:Fu Li: Mechanistic studies of Rab GTPase membrane targeting and cyc
 ling in cells
URL:https://talks-calendar.ista.ac.at/events/1233
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