PMID- 29135058
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1600-0854 (Electronic)
IS  - 1398-9219 (Linking)
VI  - 19
IP  - 2
DP  - 2018 Feb
TI  - Distinct features of multivesicular body-lysosome fusion revealed by a new 
      cell-free content-mixing assay.
PG  - 138-149
LID - 10.1111/tra.12543 [doi]
AB  - When marked for degradation, surface receptor and transporter proteins are 
      internalized and delivered to endosomes where they are packaged into intralumenal 
      vesicles (ILVs). Many rounds of ILV formation create multivesicular bodies (MVBs) 
      that fuse with lysosomes exposing ILVs to hydrolases for catabolism. Despite 
      being critical for protein degradation, the molecular underpinnings of 
      MVB-lysosome fusion remain unclear, although machinery underlying other lysosome 
      fusion events is implicated. But how then is specificity conferred? And how is 
      MVB maturation and fusion coordinated for efficient protein degradation? To 
      address these questions, we developed a cell-free MVB-lysosome fusion assay using 
      Saccharomyces cerevisiae as a model. After confirming that the Rab7 ortholog Ypt7 
      and the multisubunit tethering complex HOPS (homotypic fusion and vacuole protein 
      sorting complex) are required, we found that the Qa-SNARE Pep12 distinguishes 
      this event from homotypic lysosome fusion. Mutations that impair MVB maturation 
      block fusion by preventing Ypt7 activation, confirming that a Rab-cascade 
      mechanism harmonizes MVB maturation with lysosome fusion.
CI  - (c) 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Karim, Mahmoud Abdul
AU  - Karim MA
AD  - Department of Biology, Concordia University, Montreal, Canada.
FAU - Samyn, Dieter Ronny
AU  - Samyn DR
AD  - Department of Biology, Concordia University, Montreal, Canada.
FAU - Mattie, Sevan
AU  - Mattie S
AD  - Department of Biology, Concordia University, Montreal, Canada.
FAU - Brett, Christopher Leonard
AU  - Brett CL
AUID- ORCID: 0000-0002-0730-3405
AD  - Department of Biology, Concordia University, Montreal, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171210
PL  - England
TA  - Traffic
JT  - Traffic (Copenhagen, Denmark)
JID - 100939340
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Vesicular Transport Proteins)
RN  - EC 3.6.1.- (YPT7 protein, S cerevisiae)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
SB  - IM
MH  - Biological Transport/physiology
MH  - Cell-Free System
MH  - Endocytosis/physiology
MH  - Endosomes/*metabolism
MH  - Lysosomes/*metabolism
MH  - Membrane Fusion/physiology
MH  - Multivesicular Bodies/*metabolism
MH  - Protein Transport
MH  - Saccharomyces cerevisiae/*metabolism
MH  - Saccharomyces cerevisiae Proteins/metabolism
MH  - Vesicular Transport Proteins/metabolism
MH  - rab GTP-Binding Proteins/metabolism
OTO - NOTNLM
OT  - ESCRT
OT  - MVB
OT  - Pep12
OT  - Rab conversion
OT  - Rab-GTPase
OT  - Rab7
OT  - SNARE
OT  - Ypt7
OT  - endocytosis
OT  - lysosome
OT  - membrane fusion
OT  - multivesicular body
OT  - syntaxin
OT  - vacuole
EDAT- 2017/11/15 06:00
MHDA- 2018/12/12 06:00
CRDT- 2017/11/15 06:00
PHST- 2017/05/09 00:00 [received]
PHST- 2017/11/07 00:00 [revised]
PHST- 2017/11/09 00:00 [accepted]
PHST- 2017/11/15 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2017/11/15 06:00 [entrez]
AID - 10.1111/tra.12543 [doi]
PST - ppublish
SO  - Traffic. 2018 Feb;19(2):138-149. doi: 10.1111/tra.12543. Epub 2017 Dec 10.