Laminin chain assembly is regulated by specific coiled-coil interactions

Macdonald, Philip R.; Lustig, Ariel; Steinmetz, Michel O.; Kammerer, Richard A.

doi:10.1016/j.jsb.2010.02.004

Cited by 42 publications

(35 citation statements)

References 26 publications

(27 reference statements)

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“…The α, β, and γ subunits can be arranged either clockwise or counter clockwise when viewed down the coiled-coil axis. The order of subunits in the trimer underlies the mechanism of combinatorial assembly of laminin isotypes (35) and therefore is key to understanding the complexity and diversification of the laminin family. We reasoned that the alternative subunit arrangements could be distinguished without knowledge of the register of the three strands.…”

Section: Resultsmentioning

confidence: 99%

“…It is noteworthy that N1750 is substituted by glycine in laminin β3 chains. It has been observed that β3 forms heterodimeric assembly intermediates with γ2 but not with the γ1 or γ3 paralogs (35). The γ2 subunit differs from γ1 and γ3 at the residue immediately following the conserved Q1566, possessing an arginine instead of a glutamate.…”

Section: Resultsmentioning

confidence: 99%

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Cross-linking reveals laminin coiled-coil architecture

Armony

Jacob

Moran

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Laminin, an ∼800-kDa heterotrimeric protein, is a major functional component of the extracellular matrix, contributing to tissue development and maintenance. The unique architecture of laminin is not currently amenable to determination at high resolution, as its flexible and narrow segments complicate both crystallization and single-particle reconstruction by electron microscopy. Therefore, we used cross-linking and MS, evaluated using computational methods, to address key questions regarding laminin quaternary structure. This approach was particularly well suited to the ∼750-Å coiled coil that mediates trimer assembly, and our results support revision of the subunit order typically presented in laminin schematics. Furthermore, information on the subunit register in the coiled coil and cross-links to downstream domains provide insights into the self-assembly required for interaction with other extracellular matrix and cell surface proteins.L aminins are network-forming constituents of the extracellular matrix (ECM) (1, 2). They interact with the cell surface and other ECM components to generate a physical and functional framework affecting cell viability, identity, and activity. The laminin family appears to have arisen during the evolution of multicellularity in animals (3), and laminins contribute to a diversity of basement membrane and connective tissue structures in mammals (2). Laminins are studied in the context of development (4), stem cell biology (5), tissue engineering (6), cancer (7), and aging (8). The remarkable structural organization of laminins underlies their important physiological functions.Laminins are composed of three subunits, α, β, and γ, that assemble into a roughly humanoid form as visualized using rotary shadowing electron microscopy (9). The individual subunits separately form the "head" and two "arms," which are composed of epidermal growth factor (EGF)-like cysteine-rich repeats with globular domains embedded (10) (Fig. 1). Following the head and arms, the three subunits come together to form a long coiled coil, constituting the "body." Additional globular domains unique to the α subunit are the "feet." The laminin head and arms may splay to form a tripod (2), a feature not captured in rotary shadowing images or in diagrams of domain composition. Due to the centrality of laminin in cell-ECM interactions, efforts have been made to analyze the functional regions of the trimer, to determine which α, β, and γ paralogs associate into physiological heterotrimers and to understand how trimers self-assemble into higher-order networks. Laminin fragments have been generated to assess their binding properties (11, 12) and as targets for structure determination by X-ray crystallography (13)(14)(15)(16)(17)(18)(19)(20).Despite this progress, few insights into the overall 3D architecture of laminin have been made in the past few decades, and certain regions of the complex have been neglected as targets of structural techniques. In particular, no structure has been determined for any segment of th...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Cross-linking reveals laminin coiled-coil architecture

Armony

Jacob

Moran

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Charged residues within the heptad repeats of the coiled-coil restrict the number of allowed heterotrimers (Beck et al 1993;Macdonald et al 2010) to generate the following (confirmed) vertebrate heterotrimers: laminins-111 (i.e. a1b1g1), 121, 211, 213, 221, 311, 312, 321, 332, 411, 421, 422, 423, 511, 521, and 523 (Aumailley et al 2005;Macdonald et al 2010). The a3A subunit, which lacks the amino-terminal domains of the short arm, also exists as a longer (a3B) splice-variant with a full short arm.…”

Section: Laminin Familymentioning

confidence: 99%

Basement Membranes: Cell Scaffoldings and Signaling Platforms

Yurchenco

2010

Cold Spring Harbor Perspectives in Biology

770

775

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“…Five α, three β and three γ chains have been identified forming 16 different heterotrimers (Aumailley et al, 2005;Macdonald et al, 2010) with overlapping yet distinct tissue distribution and function (Colognato and Yurchenco, 2000;Durbeej, 2010). The current nomenclature for laminins consists of three numbers, denoting the its chain composition, e.g.…”

Section: Introductionmentioning

confidence: 99%

Laminins containing the β2 and γ3 chains regulate astrocyte migration and angiogenesis in the retina

et al. 2013

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SUMMARYPathologies of retinal blood vessels are among the major causes of blindness worldwide. A key cell type that regulates retinal vascular development is the astrocyte. Generated extrinsically to the retina, astrocytes migrate into the retina through the optic nerve head. Even though there is a strong correlation between astrocyte distribution and retinal vascular development, the factors that guide astrocytes into the retina remain unclear. In this study, we show that astrocytes migrate within a laminin-containing basement membrane -the inner limiting membrane. Genetic deletion of the laminin β2 and γ3 chains affects astrocyte migration and spatial distribution. We show that laminins act as haptotactic factors in vitro in an isoform-specific manner, inducing astrocyte migration and promoting astrocyte differentiation. The addition of exogenous laminins to laminin-null retinal explants rescues astrocyte migration and spatial patterning. Furthermore, we show that the loss of laminins reduces β1 integrin expression in astrocytes. Culturing lamininnull retinal astrocytes on laminin substrates restores focal localization of β1 integrin. Finally, we show that laminins containing β2 and γ3 chains regulate subsequent retinal blood vessel growth and maintain vascular integrity. These in vivo and in vitro studies demonstrate clearly that laminins containing β2 and γ3 chains are indispensable for migration and spatial organization of astrocytes and that they play a crucial role during retinal angiogenesis in vivo. RESEARCH ARTICLELaminins regulate angiogenesis treatment with exogenous laminins rescues astrocyte migration and spatial patterning phenotype ex vivo. Together, these data support the hypothesis that β2-and γ3-containing laminins are important cues in retinal vascular development.

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Laminin chain assembly is regulated by specific coiled-coil interactions

Cited by 42 publications

References 26 publications

Cross-linking reveals laminin coiled-coil architecture

Cross-linking reveals laminin coiled-coil architecture

Basement Membranes: Cell Scaffoldings and Signaling Platforms

Laminins containing the β2 and γ3 chains regulate astrocyte migration and angiogenesis in the retina

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