Dataset Information

Mechanistic basis for the recognition of laminin-511 by ?6?1 integrin.

ABSTRACT: Laminins regulate diverse cellular functions through interaction with integrins. Two regions of laminins-three laminin globular domains of the ? chain (LG1-3) and the carboxyl-terminal tail of the ? chain (?-tail)-are required for integrin binding, but it remains unclear how the ?-tail contributes to the binding. We determined the crystal structure of the integrin binding fragment of laminin-511, showing that the ?-tail extends to the bottom face of LG1-3. Electron microscopic imaging combined with biochemical analyses showed that integrin binds to the bottom face of LG1-3 with the ?1-tail apposed to the metal ion-dependent adhesion site (MIDAS) of integrin ?1. These findings are consistent with a model in which the ?-tail coordinates the metal ion in the MIDAS through its Glu residue.

SUBMITTER: Takizawa M

PROVIDER: S-EPMC5580876 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Mechanistic basis for the recognition of laminin-511 by α6β1 integrin.

Takizawa Mamoru M Arimori Takao T Taniguchi Yukimasa Y Kitago Yu Y Yamashita Erika E Takagi Junichi J Sekiguchi Kiyotoshi K

Science advances 20170901 9

Laminins regulate diverse cellular functions through interaction with integrins. Two regions of laminins-three laminin globular domains of the α chain (LG1-3) and the carboxyl-terminal tail of the γ chain (γ-tail)-are required for integrin binding, but it remains unclear how the γ-tail contributes to the binding. We determined the crystal structure of the integrin binding fragment of laminin-511, showing that the γ-tail extends to the bottom face of LG1-3. Electron microscopic imaging combined w ...[more]

PMID: 28879238

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Project description:Simple Summary Numerous studies over the past few decades have revealed that the interactions of gastric cancer cells with laminins through integrins play important roles in tumor cell proliferation, infiltration, and metastasis. However, the association between gastric cancer cells and the laminin E8 fragment, which is the smallest integrin-binding component, has not been investigated. In this study, we revealed that the laminin 511-E8 fragment had a greater impact on the adhesion, morphology, and proliferation of gastric cancer cells than full-length laminin 511. Thus, the laminin 511-E8 fragment is considered to be suitable for investigating the interaction between gastric cancer cells and extracellular matrices in tumor invasion and metastasis. Further, the involvement of Cdc42 in the laminin 511-E8 fragment-induced enhanced adhesion of gastric cancer cells was suggested. Abstract Background: The interaction between cancer cells and laminin (Ln) is a key event in tumor invasion and metastasis. Previously, we determined the effect of full-length Ln511 on gastric cancer cells. However, the interactions between the Ln511-E8 fragment, a truncated protein of Ln511, and gastric cancer cells have not been investigated. Methods: We investigated the adhesion properties of gastric cancer cells to full-length Ln511 and Ln511-E8 fragments. Results: The proliferation of four gastric cancer cell lines (SH-10-TC, MKN74, SC-6-JCK, and MKN45) was highest on the Ln511-E8 fragment. Further, a larger cytoplasm was observed in SH-10-TC and MKN74 cells cultured on full-length Ln511 or Ln511-E8 fragments. The percentage of adhesive cells was highest on the Ln511-E8 fragment in all four cell lines. Moreover, adhesion of the gastric cancer cells to Ln511-E8 fragment-coated plates was reduced by the Cdc42 GTPase inhibitor in a dose-dependent manner, suggesting the involvement of Cdc42 in the Ln511-E8 fragment-induced enhanced adhesion of gastric cancer cells. Conclusions: The Ln511-E8 fragment had a greater impact on the adhesion, morphology, and proliferation of gastric cancer cells than full-length laminin. Thus, the Ln511-E8 fragment is suitable for investigating the interaction between gastric cancer cells and extracellular matrices in tumor invasion and metastasis.

Dataset Information

Mechanistic basis for the recognition of laminin-511 by ?6?1 integrin.

Publications

Mechanistic basis for the recognition of laminin-511 by α6β1 integrin.

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