BEGIN:VCALENDAR VERSION:2.0 PRODID:www.dresden-science-calendar.de METHOD:PUBLISH CALSCALE:GREGORIAN X-MICROSOFT-CALSCALE:GREGORIAN X-WR-TIMEZONE:Europe/Berlin BEGIN:VTIMEZONE TZID:Europe/Berlin X-LIC-LOCATION:Europe/Berlin BEGIN:DAYLIGHT TZNAME:CEST TZOFFSETFROM:+0100 TZOFFSETTO:+0200 DTSTART:19810329T030000 RRULE:FREQ=YEARLY;INTERVAL=1;BYMONTH=3;BYDAY=-1SU END:DAYLIGHT BEGIN:STANDARD TZNAME:CET TZOFFSETFROM:+0200 TZOFFSETTO:+0100 DTSTART:19961027T030000 RRULE:FREQ=YEARLY;INTERVAL=1;BYMONTH=10;BYDAY=-1SU END:STANDARD END:VTIMEZONE BEGIN:VEVENT UID:DSC-12127 DTSTART;TZID=Europe/Berlin:20170921T110000 SEQUENCE:1506067368 TRANSP:OPAQUE DTEND;TZID=Europe/Berlin:20170921T120000 URL:https://dresden-science-calendar.de/calendar/en/detail/12127 LOCATION:MPI-CBG\, Pfotenhauerstraße 10801307 Dresden SUMMARY:Menon: Endoplasmic reticulum-plasma membrane contact sites integrat e sterol and phospholipid regulation CLASS:PUBLIC DESCRIPTION:Speaker: Anant K. Menon\nInstitute of Speaker: Weill Cornell Me dical College\, New York\, USA\nTopics:\nBiologie\n Location:\n Name: MPI -CBG (Auditorium (big half))\n Street: Pfotenhauerstraße 108\n City: 01 307 Dresden\n Phone: +49 351 210-0\n Fax: +49 351 210-2000\nDescription: Tether proteins attach the endoplasmic reticulum (ER) to other cellular m embranes thereby creating contact sites that are proposed to form platform s for regulating lipid homeostasis and facilitating non-vesicular lipid ex change. Cholesterol and its yeast counterpart ergosterol\, are synthesized in the ER and transported by non-vesicular mechanisms to the plasma membr ane (PM) where they represent almost half of all PM lipids and contribute to the barrier function of the PM. To determine whether contact sites are important for sterol exchange between the ER and PM\, we generated &\;# 8710\;-super-tether (&\;#8710\;-s-tether) yeast cells that lack six pre viously identified tethering proteins (yeast extended synatotagmins (E-Syt s)\, VAPs\, and a TMEM16-anoctamin homolog) as well as the presumptive tet her Ice2. We now show that &\;#8710\;-s-tether cells lack ER-PM contact s\, yet sustain robust ER-PM sterol exchange\, indicating that the sterol transport machinery is either absent from or not uniquely located at conta ct sites. Unexpectedly\, we found that the transport of exogenously suppli ed sterol to the ER occurs more slowly in &\;#8710\;-s-tether cells tha n in wild-type cells. We pinpointed this defect to changes in sterol organ ization and transbilayer movement within the PM bilayer caused by lipid dy sregulation\, evinced by changes in the abundance and organization of PM l ipids. Indeed\, deletion of either OSH4\, which encodes a sterol/phosphati dylinositol-4-phosphate (PI4P) exchange protein\, or the PI4P phosphatase encoded by SAC1\, caused synthetic lethality in &\;#8710\;-s-tether cel ls due to disruptions in redundant pathways regulating both PI4P and phosp holipid synthesis. The growth defect of &\;#8710\;-s-tether cells was r escued with an artificial tether assembled from unrelated non-yeast protei ns\, indicating that endogenous tether proteins play non-specific bridging functions. Finally\, we discovered that sterols play a role in regulating ER-PM contact site formation. In sterol-depleted cells\, levels of the ye ast E-Syt tether Tcb3 were induced and ER-PM contact increased dramaticall y. These results support a model in which ER-PM contact sites act as a nex us for co-ordinating the complex inter-relationship between sterols\, sphi ngolipids\, and phospholipids that maintain PM composition and integrity. DTSTAMP:20260403T203513Z CREATED:20161111T075450Z LAST-MODIFIED:20170922T080248Z END:VEVENT END:VCALENDAR