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DTSTART:20180325T030000
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DTSTART:20181028T020000
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DTSTAMP:20260403T220521Z
UID:5af1b23a383ae383035991@ist.ac.at
DTSTART:20180524T110000
DTEND:20180524T120000
DESCRIPTION:Speaker: Justine Pinskey\nhosted by Ani Kicheva\nAbstract: Hedg
 ehog (HH) signaling is essential for embryonic and postnatal development\,
  while perturbation of HH pathway function can lead to a variety of develo
 pmental diseases\, birth defects and cancer. Neuropilins\, which have well
 -characterized roles in Semaphorin and VEGF signaling\, have recently been
  implicated in the regulation of HH signaling. Neuropilins contain short\,
  catalytically inactive cytoplasmic domains\, requiring Plexin co-receptor
 s to regulate small intracellular GTPases during Semaphorin signal transdu
 ction. However\, the mechanism of Neuropilin function in HH signal transdu
 ction remains unclear\, and a role for Plexin proteins in HH signaling has
  not been explored. Using HH-dependent luciferase reporter assays in NIH/3
 T3 cells\, we show that the Neuropilin-1 cytoplasmic and transmembrane dom
 ains are both necessary and sufficient to regulate HH pathway activity\, i
 ndependently of Plexin and Semaphorin binding. Our data suggest that Neuro
 pilin-1 selectively regulates GLI activator function through a novel 12-am
 ino acid cytoplasmic motif. Strikingly\, we also find that multiple Plexin
  family members promote HH signaling. Point mutations in the GTPase activa
 ting (GAP) domain of Plexins prevent HH pathway promotion\, suggesting tha
 t GAP function is required for Plexin-dependent HH regulation. Furthermore
 \, deletion of the autoinhibitory Plexin-A1 extracellular domain significa
 ntly increases HH pathway activity\, providing additional evidence that Pl
 exin GAP activity regulates HH signaling. Together\, our data suggest that
  Neuropilins and Plexins regulate HH signaling downstream of ligand activa
 tion through distinct cytoplasmic mechanisms. Therapeutic approaches targe
 ting Semaphorin receptors may be useful to regulate overactive HH signalin
 g in cancer and other diseases.
LOCATION:Seminar Room\, Lab Building East\, ISTA
ORGANIZER:akicheva@ist.ac.at
SUMMARY:Justine Pinskey: Semaphorin Receptor Function in Hedgehog Signal Tr
 ansduction
URL:https://talks-calendar.ista.ac.at/events/1242
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