Direct interaction of the Usher syndrome 1G protein SANS and myomegalin in the retina

Autoren

Nora Overlack
Dilek Kilic
Katharina Bauß
Tina Märker
Hannie Kremer
Erwin van Wijk
Uwe Wolfrum

DOI

10.1016/j.bbamcr.2011.05.015

ISSN

0167-4889

Ausgabe der Veröffentlichung

10

Zeitschrift

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Sprache

en

Paginierung

1883 - 1892

Datum der Veröffentlichung

2011

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.bbamcr.2011.05.015

Datum der Datenerfassung

2018

Titel

Direct interaction of the Usher syndrome 1G protein SANS and myomegalin in the retina

Ausgabe der Zeitschrift

1813

Datenquelle: Crossref

Abstract

The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically heterogeneous with at least 11 chromosomal loci assigned to 3 clinical types, USH1-3. We have previously demonstrated that all USH1 and 2 proteins in the eye and the inner ear are organized into protein networks by scaffold proteins. This has contributed essentially to our current understanding of the function of USH proteins and explains why defects in proteins of different families cause very similar phenotypes. We have previously shown that the USH1G protein SANS (scaffold protein containing ankyrin repeats and SAM domain) contributes to the periciliary protein network in retinal photoreceptor cells. This study aimed to further elucidate the role of SANS by identifying novel interaction partners. In yeast two-hybrid screens of retinal cDNA libraries we identified 30 novel putative interacting proteins binding to the central domain of SANS (CENT). We confirmed the direct binding of the phosphodiesterase 4D interacting protein (PDE4DIP), a Golgi associated protein synonymously named myomegalin, to the CENT domain of SANS by independent assays. Correlative immunohistochemical and electron microscopic analyses showed a co-localization of SANS and myomegalin in mammalian photoreceptor cells in close association with microtubules. Based on the present results we propose a role of the SANS-myomegalin complex in microtubule-dependent inner segment cargo transport towards the ciliary base of photoreceptor cells.

Addresses

Institute of Zoology, Cell and Matrix Biology, Johannes Gutenberg University of Mainz, Mainz, Germany.

Autoren

Nora Overlack
Dilek Kilic
Katharina Bauss
Tina Märker
Hannie Kremer
Erwin van Wijk
Uwe Wolfrum

DOI

10.1016/j.bbamcr.2011.05.015

eISSN

1878-2434

Externe Identifier

PubMed Identifier: 21767579

Funding acknowledgements

European Commission FP7: FP7_241955

Open access

false

ISSN

0006-3002

Ausgabe der Veröffentlichung

10

Zeitschrift

Biochimica et biophysica acta

Schlüsselwörter

Retina
Cells, Cultured
COS Cells
Animals
Mice, Inbred C57BL
Cattle
Macaca mulatta
Humans
Mice
Yeasts
Adaptor Proteins, Signal Transducing
Muscle Proteins
Cytoskeletal Proteins
Nerve Tissue Proteins
Nuclear Proteins
Protein Binding
Models, Biological
Photoreceptor Cells, Vertebrate
Chlorocebus aethiops

Sprache

eng

Medium

Print-Electronic

Online publication date

2011

Paginierung

1883 - 1892

Datum der Veröffentlichung

2011

Status

Published

Datum der Datenerfassung

2011

Titel

Direct interaction of the Usher syndrome 1G protein SANS and myomegalin in the retina.

Sub types

Journal Article

Ausgabe der Zeitschrift

1813

Datenquelle: Europe PubMed Central

Abstract

The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically heterogeneous with at least 11 chromosomal loci assigned to 3 clinical types, USH1-3. We have previously demonstrated that all USH1 and 2 proteins in the eye and the inner ear are organized into protein networks by scaffold proteins. This has contributed essentially to our current understanding of the function of USH proteins and explains why defects in proteins of different families cause very similar phenotypes. We have previously shown that the USH1G protein SANS (scaffold protein containing ankyrin repeats and SAM domain) contributes to the periciliary protein network in retinal photoreceptor cells. This study aimed to further elucidate the role of SANS by identifying novel interaction partners. In yeast two-hybrid screens of retinal cDNA libraries we identified 30 novel putative interacting proteins binding to the central domain of SANS (CENT). We confirmed the direct binding of the phosphodiesterase 4D interacting protein (PDE4DIP), a Golgi associated protein synonymously named myomegalin, to the CENT domain of SANS by independent assays. Correlative immunohistochemical and electron microscopic analyses showed a co-localization of SANS and myomegalin in mammalian photoreceptor cells in close association with microtubules. Based on the present results we propose a role of the SANS-myomegalin complex in microtubule-dependent inner segment cargo transport towards the ciliary base of photoreceptor cells.

Date of acceptance

2011

Autoren

Nora Overlack
Dilek Kilic
Katharina Bauss
Tina Märker
Hannie Kremer
Erwin van Wijk
Uwe Wolfrum

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/21767579

DOI

10.1016/j.bbamcr.2011.05.015

ISSN

0006-3002

Ausgabe der Veröffentlichung

10

Zeitschrift

Biochim Biophys Acta

Schlüsselwörter

Adaptor Proteins, Signal Transducing
Animals
COS Cells
Cattle
Cells, Cultured
Chlorocebus aethiops
Cytoskeletal Proteins
Humans
Macaca mulatta
Mice
Mice, Inbred C57BL
Models, Biological
Muscle Proteins
Nerve Tissue Proteins
Nuclear Proteins
Photoreceptor Cells, Vertebrate
Protein Binding
Retina
Yeasts

Sprache

eng

Country

Netherlands

Paginierung

1883 - 1892

PII

S0167-4889(11)00186-8

Datum der Veröffentlichung

2011

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2011

Titel

Direct interaction of the Usher syndrome 1G protein SANS and myomegalin in the retina.

Sub types

Journal Article

Ausgabe der Zeitschrift

1813

Datenquelle: PubMed

Direct interaction of the Usher syndrome 1G protein SANS and myomegalin in the retina

Werkzeuge