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


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. Journal of Biological Chemistry, 279, (43), 44504-44512. (doi:10.1074/jbc.M402455200).

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Original Publication URL: http://dx.doi.org/10.1074/jbc.M402455200

Description/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 ,
, and chains in different laminin molecules with homologous
interactions being insignificant. The laminin
family consists of 15 known isoforms formed from five ,
three , and three 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 chains and from the 2 and
3 subunits. The chain-derived LN domains showed a
far more limited binding repertoire, particularly in the
case of the 3 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.

Item Type: Article
ISSNs: 0021-9258 (print)
Related URLs:
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 37530
Date Deposited: 25 May 2006
Last Modified: 27 Mar 2014 18:23
URI: http://eprints.soton.ac.uk/id/eprint/37530

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