The University of Southampton
University of Southampton Institutional Repository

Molecular analysis of laminin N-terminal domains mediating self-interactions

Molecular analysis of laminin N-terminal domains mediating self-interactions
Molecular analysis of laminin N-terminal domains mediating self-interactions
The ability of laminins to self-polymerize is crucial for the formation of basement membranes. Development of this polymerized network has profound effects upon tissue architecture as well as on the intracellular organization and differentiation of neighboring cells. The laminin N-terminal (LN) domains have been shown to mediate this interaction and studies using proteolytic fragments derived from laminin-1 led to the theory that network assembly depends on the formation of a heterotrimeric complex between LN domains derived from α, β, and γ chains in different laminin molecules with homologous interactions being insignificant. The laminin family consists of 15 known isoforms formed from five α, three β, and three γ chains, of which some are truncated and lack the N-terminal LN domain. To address whether the model of heterotrimeric complex formation is applicable to laminin isoforms other than laminin-1, eight LN domains found in the laminin protein family were recombinantly expressed and tested in three different assays for homologous and heterologous interactions. The results showed that the lack of homologous interactions is an exception, with such interactions being seen for LN domains derived from all α chains and from the β2 and β3 subunits. The γ chain-derived LN domains showed a far more limited binding repertoire, particularly in the case of the γ3 chain, which is found present in a range of non-basement membrane locations. Further, whereas the interactions depended upon Ca2+ ions, with EDTA reversibly abrogating binding, EDTA-induced conformational changes were not reversible. Together these results demonstrate that the assembly model proposed on the basis of laminin-1 may be a simplification, with the assembly of naturally occurring laminin networks being far more complex and highly dependent upon which laminin isoforms are present.
0021-9258
44504-44512
Odenthal, Uwe
2f6ee94e-e4d8-4b8f-ac7d-97fb76d38eac
Haehn, Sebastian
960fe417-6b58-465d-9745-b83488a68ac8
Tunggal, Patrick
41a5bed8-8f38-4358-ac6d-7d780683a637
Merkl, Barbara
d2a911be-d3d6-4cd3-a1ba-91de810b9502
Schomburg, Dietmar
b8235e02-5546-4559-9649-0afed7485c1b
Frie, Christian
f6f99d99-b55f-433c-bbde-2ea251688719
Paulsson, Mats
6b6500dc-6e7c-477b-96be-8ebdf82224bf
Smyth, Neil
0eba2a40-3b43-4d40-bb64-621bd7e9d505
Odenthal, Uwe
2f6ee94e-e4d8-4b8f-ac7d-97fb76d38eac
Haehn, Sebastian
960fe417-6b58-465d-9745-b83488a68ac8
Tunggal, Patrick
41a5bed8-8f38-4358-ac6d-7d780683a637
Merkl, Barbara
d2a911be-d3d6-4cd3-a1ba-91de810b9502
Schomburg, Dietmar
b8235e02-5546-4559-9649-0afed7485c1b
Frie, Christian
f6f99d99-b55f-433c-bbde-2ea251688719
Paulsson, Mats
6b6500dc-6e7c-477b-96be-8ebdf82224bf
Smyth, Neil
0eba2a40-3b43-4d40-bb64-621bd7e9d505

Odenthal, Uwe, Haehn, Sebastian, Tunggal, Patrick, Merkl, Barbara, Schomburg, Dietmar, Frie, Christian, Paulsson, Mats and Smyth, Neil (2004) Molecular analysis of laminin N-terminal domains mediating self-interactions. The Journal of Biological Chemistry, 279 (43), 44504-44512. (doi:10.1074/jbc.M402455200).

Record type: Article

Abstract

The ability of laminins to self-polymerize is crucial for the formation of basement membranes. Development of this polymerized network has profound effects upon tissue architecture as well as on the intracellular organization and differentiation of neighboring cells. The laminin N-terminal (LN) domains have been shown to mediate this interaction and studies using proteolytic fragments derived from laminin-1 led to the theory that network assembly depends on the formation of a heterotrimeric complex between LN domains derived from α, β, and γ chains in different laminin molecules with homologous interactions being insignificant. The laminin family consists of 15 known isoforms formed from five α, three β, and three γ chains, of which some are truncated and lack the N-terminal LN domain. To address whether the model of heterotrimeric complex formation is applicable to laminin isoforms other than laminin-1, eight LN domains found in the laminin protein family were recombinantly expressed and tested in three different assays for homologous and heterologous interactions. The results showed that the lack of homologous interactions is an exception, with such interactions being seen for LN domains derived from all α chains and from the β2 and β3 subunits. The γ chain-derived LN domains showed a far more limited binding repertoire, particularly in the case of the γ3 chain, which is found present in a range of non-basement membrane locations. Further, whereas the interactions depended upon Ca2+ ions, with EDTA reversibly abrogating binding, EDTA-induced conformational changes were not reversible. Together these results demonstrate that the assembly model proposed on the basis of laminin-1 may be a simplification, with the assembly of naturally occurring laminin networks being far more complex and highly dependent upon which laminin isoforms are present.

Text
odenthal.pdf - Version of Record
Restricted to Registered users only
Download (442kB)
Request a copy

More information

Submitted date: 4 March 2004
Published date: 22 October 2004

Identifiers

Local EPrints ID: 37530
URI: http://eprints.soton.ac.uk/id/eprint/37530
ISSN: 0021-9258
PURE UUID: 52837d82-7df3-46ad-9968-4c439a744ea4

Catalogue record

Date deposited: 25 May 2006
Last modified: 08 Jan 2022 18:57

Export record

Altmetrics

Contributors

Author: Uwe Odenthal
Author: Sebastian Haehn
Author: Patrick Tunggal
Author: Barbara Merkl
Author: Dietmar Schomburg
Author: Christian Frie
Author: Mats Paulsson
Author: Neil Smyth

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×