The retinitis pigmentosa 28 protein FAM161A is a novel ciliary protein involved in intermolecular protein interaction and microtubule association

Publication type:
Journal article
Metadata:
Autoren
  • Frank Zach
  • Felix Grassmann
  • Thomas Langmann
  • Nasrin Sorusch
  • Uwe Wolfrum
  • Heidi Stöhr
DOI
10.1093/hmg/dds268
eISSN
1460-2083
ISSN
0964-6906
Ausgabe der Veröffentlichung
21
Zeitschrift
Human Molecular Genetics
Sprache
en
Online publication date
2012
Paginierung
4573 - 4586
Datum der Veröffentlichung
2012
Status
Published
Herausgeber
Oxford University Press (OUP)
Herausgeber URL
http://dx.doi.org/10.1093/hmg/dds268
Datum der Datenerfassung
2022
Titel
The retinitis pigmentosa 28 protein FAM161A is a novel ciliary protein involved in intermolecular protein interaction and microtubule association
Ausgabe der Zeitschrift
21

Data source: Crossref

Other metadata sources:
Abstract
Loss-of-function mutations in the gene encoding FAM161A were recently discovered as the cause for RP28, an autosomal recessive form of retinitis pigmentosa. To initiate the characterization of the cellular role of FAM161A in the retina, we focused on its subcellular localization and conducted in vitro studies to identify FAM161A-interacting proteins and associated cellular structures. Immunohistochemistry revealed the presence of mouse FAM161A in the photoreceptor inner segments, the synaptic regions of the outer and inner plexiform layers and the ganglion cells. In mouse and human retinal sections from unfixed eyes, FAM161A localized to the ciliary region linking photoreceptor outer and inner segments. High-resolution immunofluorescence and immunoelectron microscopy mapped FAM161A to the connecting cilium, the basal body region and the adjacent centriole. Ectopic FAM161A was found in the centrosome and concentrated at the base of primary cilia in cultured cells. In addition, overexpressed FAM161A was clearly associated with microtubules during interphase and mitosis. The presence of FAM161A increased microtubule acetylation and stabilization. We further show that the evolutionarily conserved UPF0564 domain of FAM161A is crucial for its binding to microtubules and mediates homo- and heterotypic FAM161A and FAM161B interaction. In conclusion, our study shows that FAM161A is a microtubule-associated ciliary protein presumably involved in microtubule stabilization to maintain the microtubule tracks and/or in transport processes along microtubules in photoreceptors and other retinal cell types.
Addresses
  • Institute of Human Genetics, University of Regensburg, Regensburg, Germany.
Autoren
  • Frank Zach
  • Felix Grassmann
  • Thomas Langmann
  • Nasrin Sorusch
  • Uwe Wolfrum
  • Heidi Stöhr
DOI
10.1093/hmg/dds268
eISSN
1460-2083
Externe Identifier
  • PubMed Identifier: 22791751
Open access
false
ISSN
0964-6906
Ausgabe der Veröffentlichung
21
Zeitschrift
Human molecular genetics
Schlüsselwörter
  • Retina
  • Centrosome
  • Microtubules
  • Animals
  • Humans
  • Mice
  • Retinitis Pigmentosa
  • Eye Proteins
  • Mutation
  • Photoreceptor Cells
Sprache
eng
Medium
Print-Electronic
Online publication date
2012
Paginierung
4573 - 4586
Datum der Veröffentlichung
2012
Status
Published
Datum der Datenerfassung
2012
Titel
The retinitis pigmentosa 28 protein FAM161A is a novel ciliary protein involved in intermolecular protein interaction and microtubule association.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
21

Data source: Europe PubMed Central

Abstract
Loss-of-function mutations in the gene encoding FAM161A were recently discovered as the cause for RP28, an autosomal recessive form of retinitis pigmentosa. To initiate the characterization of the cellular role of FAM161A in the retina, we focused on its subcellular localization and conducted in vitro studies to identify FAM161A-interacting proteins and associated cellular structures. Immunohistochemistry revealed the presence of mouse FAM161A in the photoreceptor inner segments, the synaptic regions of the outer and inner plexiform layers and the ganglion cells. In mouse and human retinal sections from unfixed eyes, FAM161A localized to the ciliary region linking photoreceptor outer and inner segments. High-resolution immunofluorescence and immunoelectron microscopy mapped FAM161A to the connecting cilium, the basal body region and the adjacent centriole. Ectopic FAM161A was found in the centrosome and concentrated at the base of primary cilia in cultured cells. In addition, overexpressed FAM161A was clearly associated with microtubules during interphase and mitosis. The presence of FAM161A increased microtubule acetylation and stabilization. We further show that the evolutionarily conserved UPF0564 domain of FAM161A is crucial for its binding to microtubules and mediates homo- and heterotypic FAM161A and FAM161B interaction. In conclusion, our study shows that FAM161A is a microtubule-associated ciliary protein presumably involved in microtubule stabilization to maintain the microtubule tracks and/or in transport processes along microtubules in photoreceptors and other retinal cell types.
Autoren
  • Frank Zach
  • Felix Grassmann
  • Thomas Langmann
  • Nasrin Sorusch
  • Uwe Wolfrum
  • Heidi Stöhr
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/22791751
DOI
10.1093/hmg/dds268
eISSN
1460-2083
Ausgabe der Veröffentlichung
21
Zeitschrift
Hum Mol Genet
Schlüsselwörter
  • Animals
  • Centrosome
  • Eye Proteins
  • Humans
  • Mice
  • Microtubules
  • Mutation
  • Photoreceptor Cells
  • Retina
  • Retinitis Pigmentosa
Sprache
eng
Country
England
Paginierung
4573 - 4586
PII
dds268
Datum der Veröffentlichung
2012
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2013
Titel
The retinitis pigmentosa 28 protein FAM161A is a novel ciliary protein involved in intermolecular protein interaction and microtubule association.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
21

Data source: PubMed

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