PMID- 10562279
OWN - NLM
STAT- MEDLINE
DCOM- 19991217
LR  - 20191023
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 147
IP  - 4
DP  - 1999 Nov 15
TI  - PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in
      peroxisomal matrix protein import.
PG  - 761-74
AB  - Peroxisomal matrix protein import requires PEX12, an integral peroxisomal
      membrane protein with a zinc ring domain at its carboxy terminus. Mutations in
      human PEX12 result in Zellweger syndrome, a lethal neurological disorder, and
      implicate the zinc ring domain in PEX12 function. Using two-hybrid studies, blot 
      overlay assays, and coimmunoprecipitation experiments, we observed that the
      zinc-binding domain of PEX12 binds both PEX5, the PTS1 receptor, and PEX10,
      another integral peroxisomal membrane protein required for peroxisomal matrix
      protein import. Furthermore, we identified a patient with a missense mutation in 
      the PEX12 zinc-binding domain, S320F, and observed that this mutation reduces the
      binding of PEX12 to PEX5 and PEX10. Overexpression of either PEX5 or PEX10 can
      suppress this PEX12 mutation, providing genetic evidence that these interactions 
      are biologically relevant. PEX5 is a predominantly cytoplasmic protein and
      previous PEX5-binding proteins have been implicated in docking PEX5 to the
      peroxisome surface. However, we find that loss of PEX12 or PEX10 does not reduce 
      the association of PEX5 with peroxisomes, demonstrating that these peroxins are
      not required for receptor docking. These and other results lead us to propose
      that PEX12 and PEX10 play direct roles in peroxisomal matrix protein import
      downstream of the receptor docking event.
FAU - Chang, C C
AU  - Chang CC
AD  - The Department of Biological Chemistry, The Johns Hopkins University School of
      Medicine, Baltimore, Maryland 21205, USA.
FAU - Warren, D S
AU  - Warren DS
FAU - Sacksteder, K A
AU  - Sacksteder KA
FAU - Gould, S J
AU  - Gould SJ
LA  - eng
GR  - DK45787/DK/NIDDK NIH HHS/United States
GR  - HD10987/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (DNA Primers)
RN  - 0 (Membrane Proteins)
RN  - 0 (PEX10 protein, human)
RN  - 0 (PEX12 protein, human)
RN  - 0 (PEX5 protein, human)
RN  - 0 (Peroxins)
RN  - 0 (Peroxisome-Targeting Signal 1 Receptor)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Recombinant Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Cell Line
MH  - DNA/genetics
MH  - DNA Primers
MH  - Humans
MH  - Membrane Proteins/chemistry/*genetics/*metabolism
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Open Reading Frames
MH  - Peroxins
MH  - Peroxisomal Disorders/genetics/metabolism/pathology
MH  - Peroxisome-Targeting Signal 1 Receptor
MH  - Peroxisomes/*metabolism
MH  - Point Mutation
MH  - Protein Binding
MH  - Protein Biosynthesis
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Repetitive Sequences, Amino Acid
MH  - Repetitive Sequences, Nucleic Acid
MH  - Skin/metabolism/pathology
MH  - Transfection
MH  - Zellweger Syndrome/genetics
PMC - PMC2156163
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1083/jcb.147.4.761 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Nov 15;147(4):761-74. doi: 10.1083/jcb.147.4.761.