The laminin α chains: Expression, developmental transitions, and chromosomal locations of α1-5, identification of heterotrimeric laminins 8- 11, and cloning of a novel α3 isoform

Jeffrey H. Miner, Bruce Patton, Stephen I. Lentz, Debra J. Gilbert, William D. Snider, Nancy A. Jenkins, Neal G. Copeland, Joshua R. Sanes

Research output: Contribution to journalArticle

547 Citations (Scopus)

Abstract

Laminin trimers composed of α, β, and γ chains are major components of basal laminae (BLs) throughout the body. To date, three α chains (α1-3) have been shown to assemble into at least seven heterotrimers (called laminins 1-7). Genes encoding two additional α chains (α4 and α5) have been cloned, but little is known about their expression, and their protein products have not been identified. Here we generated antisera to recombinant α4 and α5 and used them to identify authentic proteins in tissue extracts. Immunoprecipitation and immunoblotting showed that α4 and α5 assemble into four novel laminin heterotrimers (laminins 8-11: α4β1γ1, α4β2γ1, α5β1γ1, and α5β2γ1, respectively). Using a panel of nucleotide and antibody probes, we surveyed the expression of α1-5 in murine tissues. All five chains were expressed in both embryos and adults, but each was distributed in a distinct pattern at both RNA and protein levels. Overall, α4 and α5 exhibited the broadest patterns of expression, while expression of α1 was the most restricted. Immunohistochemical analysis of kidney, lung, and heart showed that the α chains were confined to extracellular matrix and, with few exceptions, to BLs. All developing and adult BLs examined contained at least one α chain, all α chains were present in multiple BLs, and some BLs contained two or three α chains. Detailed analysis of developing kidney revealed that some individual BLs, including those of the tubule and glomerulus, changed in laminin chain composition as they matured, expressing up to three different α chains and two different β chains in an elaborate and dynamic progression. Interspecific backcross mapping of the five, chain genes revealed that they are distributed on four mouse chromosomes. Finally, we identified a novel full-length α3 isoform encoded by the Lama3 gene, which was previously believed to encode only truncated chains. Together, these results reveal remarkable diversity in BL composition and complexity in BL development.

Original languageEnglish (US)
Pages (from-to)685-701
Number of pages17
JournalJournal of Cell Biology
Volume137
Issue number3
DOIs
StatePublished - May 5 1997
Externally publishedYes

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Laminin
Basement Membrane
Organism Cloning
Protein Isoforms
Genes
Kidney
Proteins
Tissue Extracts
laminin 8
Immunoprecipitation
Immunoblotting
Extracellular Matrix
Immune Sera
Embryonic Structures
Nucleotides
Chromosomes
RNA
Lung
Antibodies

ASJC Scopus subject areas

  • Cell Biology

Cite this

The laminin α chains : Expression, developmental transitions, and chromosomal locations of α1-5, identification of heterotrimeric laminins 8- 11, and cloning of a novel α3 isoform. / Miner, Jeffrey H.; Patton, Bruce; Lentz, Stephen I.; Gilbert, Debra J.; Snider, William D.; Jenkins, Nancy A.; Copeland, Neal G.; Sanes, Joshua R.

In: Journal of Cell Biology, Vol. 137, No. 3, 05.05.1997, p. 685-701.

Research output: Contribution to journalArticle

Miner, Jeffrey H. ; Patton, Bruce ; Lentz, Stephen I. ; Gilbert, Debra J. ; Snider, William D. ; Jenkins, Nancy A. ; Copeland, Neal G. ; Sanes, Joshua R. / The laminin α chains : Expression, developmental transitions, and chromosomal locations of α1-5, identification of heterotrimeric laminins 8- 11, and cloning of a novel α3 isoform. In: Journal of Cell Biology. 1997 ; Vol. 137, No. 3. pp. 685-701.
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abstract = "Laminin trimers composed of α, β, and γ chains are major components of basal laminae (BLs) throughout the body. To date, three α chains (α1-3) have been shown to assemble into at least seven heterotrimers (called laminins 1-7). Genes encoding two additional α chains (α4 and α5) have been cloned, but little is known about their expression, and their protein products have not been identified. Here we generated antisera to recombinant α4 and α5 and used them to identify authentic proteins in tissue extracts. Immunoprecipitation and immunoblotting showed that α4 and α5 assemble into four novel laminin heterotrimers (laminins 8-11: α4β1γ1, α4β2γ1, α5β1γ1, and α5β2γ1, respectively). Using a panel of nucleotide and antibody probes, we surveyed the expression of α1-5 in murine tissues. All five chains were expressed in both embryos and adults, but each was distributed in a distinct pattern at both RNA and protein levels. Overall, α4 and α5 exhibited the broadest patterns of expression, while expression of α1 was the most restricted. Immunohistochemical analysis of kidney, lung, and heart showed that the α chains were confined to extracellular matrix and, with few exceptions, to BLs. All developing and adult BLs examined contained at least one α chain, all α chains were present in multiple BLs, and some BLs contained two or three α chains. Detailed analysis of developing kidney revealed that some individual BLs, including those of the tubule and glomerulus, changed in laminin chain composition as they matured, expressing up to three different α chains and two different β chains in an elaborate and dynamic progression. Interspecific backcross mapping of the five, chain genes revealed that they are distributed on four mouse chromosomes. Finally, we identified a novel full-length α3 isoform encoded by the Lama3 gene, which was previously believed to encode only truncated chains. Together, these results reveal remarkable diversity in BL composition and complexity in BL development.",
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