MPP1 links the Usher protein network and the Crumbs protein complex in the retina

Autoren

I Gosens
E van Wijk
FFJ Kersten
E Krieger
B van der Zwaag
T Marker
SJF Letteboer
S Dusseljee
T Peters
HA Spierenburg
IM Punte
U Wolfrum
FPM Cremers
H Kremer
R Roepman

DOI

10.1093/hmg/ddm147

eISSN

1460-2083

ISSN

0964-6906

Ausgabe der Veröffentlichung

16

Zeitschrift

Human Molecular Genetics

Sprache

en

Online publication date

2007

Paginierung

1993 - 2003

Status

Published online

Herausgeber

Oxford University Press (OUP)

Herausgeber URL

http://dx.doi.org/10.1093/hmg/ddm147

Datum der Datenerfassung

2017

Titel

MPP1 links the Usher protein network and the Crumbs protein complex in the retina

Ausgabe der Zeitschrift

16

Datenquelle: Crossref

Abstract

The highly ordered distribution of neurons is an essential feature of a functional mammalian retina. Disruptions in the apico-basal polarity complexes at the outer limiting membrane (OLM) of the retina are associated with retinal patterning defects in vertebrates. We have analyzed the binding repertoire of MPP5/Pals1, a key member of the apico-basal Crumbs polarity complex, that has functionally conserved counterparts in zebrafish (nagie oko) and Drosophila (Stardust). We show that MPP5 interacts with its MAGUK family member MPP1/p55 at the OLM. Mechanistically, this interaction involves heterodimerization of both MAGUK modules in a directional fashion. MPP1 expression in the retina throughout development resembles the expression of whirlin, a multi-PDZ scaffold protein and an important organizer in the Usher protein network. We demonstrate that both proteins interact strongly by both a classical PDZ domain-to-PDZ binding motif (PBM) mechanism, and a mechanism involving internal epitopes. MPP1 and whirlin colocalize in the retina at the OLM, at the outer synaptic layer and at the basal bodies and the ciliary axoneme. In view of the known roles of the Crumbs and Usher protein networks, our findings suggest a novel link of the core developmental processes of actin polymerization and establishment/maintenance of apico-basal cell polarity through MPP1. These processes, essential in neural development and patterning of the retina, may be disrupted in eye disorders that are associated with defects in these protein networks.

Addresses

Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Autoren

Ilse Gosens
Erwin van Wijk
Ferry FJ Kersten
Elmar Krieger
Bert van der Zwaag
Tina Märker
Stef JF Letteboer
Simone Dusseljee
Theo Peters
Henk A Spierenburg
Ingrid M Punte
Uwe Wolfrum
Frans PM Cremers
Hannie Kremer
Ronald Roepman

DOI

10.1093/hmg/ddm147

eISSN

1460-2083

Externe Identifier

PubMed Identifier: 17584769

Open access

false

ISSN

0964-6906

Ausgabe der Veröffentlichung

16

Zeitschrift

Human molecular genetics

Schlüsselwörter

Retina
Cell Membrane
Animals
Mice, Transgenic
Humans
Mice
Rats
Rats, Wistar
Nucleoside-Phosphate Kinase
Blood Proteins
Eye Proteins
Membrane Proteins
Nerve Tissue Proteins
Extracellular Matrix Proteins
Two-Hybrid System Techniques
Binding Sites
Amino Acid Sequence
Protein Structure, Tertiary
Models, Biological
Models, Genetic
Molecular Sequence Data
Embryo, Mammalian

Sprache

eng

Medium

Print-Electronic

Online publication date

2007

Paginierung

1993 - 2003

Datum der Veröffentlichung

2007

Status

Published

Datum der Datenerfassung

2007

Titel

MPP1 links the Usher protein network and the Crumbs protein complex in the retina.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

16

Datenquelle: Europe PubMed Central

Abstract

The highly ordered distribution of neurons is an essential feature of a functional mammalian retina. Disruptions in the apico-basal polarity complexes at the outer limiting membrane (OLM) of the retina are associated with retinal patterning defects in vertebrates. We have analyzed the binding repertoire of MPP5/Pals1, a key member of the apico-basal Crumbs polarity complex, that has functionally conserved counterparts in zebrafish (nagie oko) and Drosophila (Stardust). We show that MPP5 interacts with its MAGUK family member MPP1/p55 at the OLM. Mechanistically, this interaction involves heterodimerization of both MAGUK modules in a directional fashion. MPP1 expression in the retina throughout development resembles the expression of whirlin, a multi-PDZ scaffold protein and an important organizer in the Usher protein network. We demonstrate that both proteins interact strongly by both a classical PDZ domain-to-PDZ binding motif (PBM) mechanism, and a mechanism involving internal epitopes. MPP1 and whirlin colocalize in the retina at the OLM, at the outer synaptic layer and at the basal bodies and the ciliary axoneme. In view of the known roles of the Crumbs and Usher protein networks, our findings suggest a novel link of the core developmental processes of actin polymerization and establishment/maintenance of apico-basal cell polarity through MPP1. These processes, essential in neural development and patterning of the retina, may be disrupted in eye disorders that are associated with defects in these protein networks.

Autoren

Ilse Gosens
Erwin van Wijk
Ferry FJ Kersten
Elmar Krieger
Bert van der Zwaag
Tina Märker
Stef JF Letteboer
Simone Dusseljee
Theo Peters
Henk A Spierenburg
Ingrid M Punte
Uwe Wolfrum
Frans PM Cremers
Hannie Kremer
Ronald Roepman

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/17584769

DOI

10.1093/hmg/ddm147

ISSN

0964-6906

Ausgabe der Veröffentlichung

16

Zeitschrift

Hum Mol Genet

Schlüsselwörter

Amino Acid Sequence
Animals
Binding Sites
Blood Proteins
Cell Membrane
Embryo, Mammalian
Extracellular Matrix Proteins
Eye Proteins
Humans
Membrane Proteins
Mice
Mice, Transgenic
Models, Biological
Models, Genetic
Molecular Sequence Data
Nerve Tissue Proteins
Nucleoside-Phosphate Kinase
Protein Structure, Tertiary
Rats
Rats, Wistar
Retina
Two-Hybrid System Techniques

Sprache

eng

Country

England

Paginierung

1993 - 2003

PII

ddm147

Datum der Veröffentlichung

2007

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2007

Titel

MPP1 links the Usher protein network and the Crumbs protein complex in the retina.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

16

Datenquelle: PubMed

MPP1 links the Usher protein network and the Crumbs protein complex in the retina

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