dc.contributor.author |
O'Toole, JF |
|
dc.contributor.author |
Liu, Y |
|
dc.contributor.author |
Davis, EE |
|
dc.contributor.author |
Westlake, CJ |
|
dc.contributor.author |
Attanasio, M |
|
dc.contributor.author |
Otto, EA |
|
dc.contributor.author |
Seelow, D |
|
dc.contributor.author |
Nurnberg, G |
|
dc.contributor.author |
Becker, C |
|
dc.contributor.author |
Nuutinen, M |
|
dc.contributor.author |
Kärppä, M |
|
dc.contributor.author |
Ignatius, J |
|
dc.contributor.author |
Uusimaa, J |
|
dc.contributor.author |
Pakanen, S |
|
dc.contributor.author |
Jaakkola, E |
|
dc.contributor.author |
van den Heuvel, LP |
|
dc.contributor.author |
Fehrenbach, H |
|
dc.contributor.author |
Wiggins, R |
|
dc.contributor.author |
Goyal, M |
|
dc.contributor.author |
Zhou, W |
|
dc.contributor.author |
Wolf, MT |
|
dc.contributor.author |
Wise, E |
|
dc.contributor.author |
Helou, J |
|
dc.contributor.author |
Allen, SJ |
|
dc.contributor.author |
Murga Zamalloa, CA |
|
dc.contributor.author |
Ashraf, S |
|
dc.contributor.author |
Chaki, M |
|
dc.contributor.author |
Heeringa, S |
|
dc.contributor.author |
Chernin, G |
|
dc.contributor.author |
Hoskins, BE |
|
dc.contributor.author |
Chaib, H |
|
dc.contributor.author |
Gleeson, J |
|
dc.contributor.author |
Kusakabe, T |
|
dc.contributor.author |
Suzuki, T |
|
dc.contributor.author |
Isaac, RE |
|
dc.contributor.author |
Quarmby, LM |
|
dc.contributor.author |
Tennant, B |
|
dc.contributor.author |
Fujioka, H |
|
dc.contributor.author |
Tuominen, H |
|
dc.contributor.author |
Hassinen, I |
|
dc.contributor.author |
Lohi, H |
|
dc.contributor.author |
van Houten, JL |
|
dc.contributor.author |
Rotig, A |
|
dc.contributor.author |
Sayer, JA |
|
dc.contributor.author |
Rolinski, B |
|
dc.contributor.author |
Freisinger, P |
|
dc.contributor.author |
Madhavan, SM |
|
dc.contributor.author |
Herzer, M |
|
dc.contributor.author |
Madignier, F |
|
dc.contributor.author |
Prokisch, H |
|
dc.contributor.author |
Nurnberg, P |
|
dc.contributor.author |
Jackson, PK |
|
dc.contributor.author |
Jackson, P |
|
dc.contributor.author |
Khanna, H |
|
dc.contributor.author |
Katsanis, N |
|
dc.contributor.author |
Hildebrandt, F |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2011-06-21T17:27:54Z |
|
dc.date.issued |
2010-03 |
|
dc.identifier |
http://www.ncbi.nlm.nih.gov/pubmed/20179356 |
|
dc.identifier |
40076 |
|
dc.identifier.uri |
https://hdl.handle.net/10161/4325 |
|
dc.description.abstract |
The autosomal recessive kidney disease nephronophthisis (NPHP) constitutes the most
frequent genetic cause of terminal renal failure in the first 3 decades of life. Ten
causative genes (NPHP1-NPHP9 and NPHP11), whose products localize to the primary cilia-centrosome
complex, support the unifying concept that cystic kidney diseases are "ciliopathies".
Using genome-wide homozygosity mapping, we report here what we believe to be a new
locus (NPHP-like 1 [NPHPL1]) for an NPHP-like nephropathy. In 2 families with an NPHP-like
phenotype, we detected homozygous frameshift and splice-site mutations, respectively,
in the X-prolyl aminopeptidase 3 (XPNPEP3) gene. In contrast to all known NPHP proteins,
XPNPEP3 localizes to mitochondria of renal cells. However, in vivo analyses also revealed
a likely cilia-related function; suppression of zebrafish xpnpep3 phenocopied the
developmental phenotypes of ciliopathy morphants, and this effect was rescued by human
XPNPEP3 that was devoid of a mitochondrial localization signal. Consistent with a
role for XPNPEP3 in ciliary function, several ciliary cystogenic proteins were found
to be XPNPEP3 substrates, for which resistance to N-terminal proline cleavage resulted
in attenuated protein function in vivo in zebrafish. Our data highlight an emerging
link between mitochondria and ciliary dysfunction, and suggest that further understanding
the enzymatic activity and substrates of XPNPEP3 will illuminate novel cystogenic
pathways.
|
|
dc.language |
eng |
|
dc.language.iso |
en_US |
|
dc.publisher |
American Society for Clinical Investigation |
|
dc.relation.ispartof |
J Clin Invest |
|
dc.relation.isversionof |
10.1172/JCI40076 |
|
dc.subject |
Aminopeptidases |
|
dc.subject |
Animals |
|
dc.subject |
Centrosome |
|
dc.subject |
Chromosome Mapping |
|
dc.subject |
Cilia |
|
dc.subject |
Family |
|
dc.subject |
Female |
|
dc.subject |
Genetic Diseases, Inborn |
|
dc.subject |
Genome-Wide Association Study |
|
dc.subject |
Humans |
|
dc.subject |
Kidney |
|
dc.subject |
Male |
|
dc.subject |
Mitochondria |
|
dc.subject |
Mitochondrial Proteins |
|
dc.subject |
Rats |
|
dc.subject |
Rats, Sprague-Dawley |
|
dc.subject |
Renal Insufficiency |
|
dc.subject |
Zebrafish |
|
dc.title |
Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop
a nephronophthisis-like nephropathy.
|
|
dc.title.alternative |
|
|
dc.type |
Journal article |
|
duke.contributor.id |
Davis, EE|0520136 |
|
duke.contributor.id |
Zhou, W|0812546 |
|
duke.contributor.id |
Katsanis, N|0510002 |
|
dc.description.version |
Version of Record |
|
duke.date.pubdate |
2010-3-0 |
|
duke.description.issue |
3 |
|
duke.description.volume |
120 |
|
dc.relation.journal |
Journal of Clinical Investigation |
|
pubs.author-url |
http://www.ncbi.nlm.nih.gov/pubmed/20179356 |
|
pubs.begin-page |
791 |
|
pubs.end-page |
802 |
|
pubs.issue |
3 |
|
pubs.organisational-group |
Basic Science Departments |
|
pubs.organisational-group |
Cell Biology |
|
pubs.organisational-group |
Clinical Science Departments |
|
pubs.organisational-group |
Duke |
|
pubs.organisational-group |
Duke Cancer Institute |
|
pubs.organisational-group |
Institutes and Centers |
|
pubs.organisational-group |
Pediatrics |
|
pubs.organisational-group |
Pediatrics, Neonatology |
|
pubs.organisational-group |
School of Medicine |
|
pubs.publication-status |
Published |
|
pubs.volume |
120 |
|
dc.identifier.eissn |
1558-8238 |
|
duke.contributor.orcid |
Davis, EE|0000-0002-2412-8397 |
|