Kindlin-1 regulates integrin dynamics and adhesion turnover.
Loss-of-function mutations in the gene encoding the integrin co-activator kindlin-1 cause Kindler syndrome. We report a novel kindlin-1-deficient keratinocyte cell line derived from a Kindler syndrome patient. Despite the expression of kindlin-2, the patient's cells display several hallmarks re...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3679067?pdf=render |
| _version_ | 1811226304320634880 |
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| author | Coert Margadant Maaike Kreft Giovanna Zambruno Arnoud Sonnenberg |
| author_facet | Coert Margadant Maaike Kreft Giovanna Zambruno Arnoud Sonnenberg |
| author_sort | Coert Margadant |
| collection | DOAJ |
| description | Loss-of-function mutations in the gene encoding the integrin co-activator kindlin-1 cause Kindler syndrome. We report a novel kindlin-1-deficient keratinocyte cell line derived from a Kindler syndrome patient. Despite the expression of kindlin-2, the patient's cells display several hallmarks related to reduced function of β1 integrins, including abnormal cell morphology, cell adhesion, cell spreading, focal adhesion assembly, and cell migration. Defective cell adhesion was aggravated by kindlin-2 depletion, indicating that kindlin-2 can compensate to a certain extent for the loss of kindlin-1. Intriguingly, β1 at the cell-surface was aberrantly glycosylated in the patient's cells, and its expression was considerably reduced, both in cells in vitro and in the patient's epidermis. Reconstitution with wild-type kindlin-1 but not with a β1-binding defective mutant restored the aberrant β1 expression and glycosylation, and normalized cell morphology, adhesion, spreading, and migration. Furthermore, the expression of wild-type kindlin-1, but not of the integrin-binding-defective mutant, increased the stability of integrin-mediated cell-matrix adhesions and enhanced the redistribution of internalized integrins to the cell surface. Thus, these data uncover a role for kindlin-1 in the regulation of integrin trafficking and adhesion turnover. |
| first_indexed | 2024-04-12T09:22:57Z |
| format | Article |
| id | doaj.art-aa8465d1c16c40229262f64f621f972c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T09:22:57Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-aa8465d1c16c40229262f64f621f972c2022-12-22T03:38:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6534110.1371/journal.pone.0065341Kindlin-1 regulates integrin dynamics and adhesion turnover.Coert MargadantMaaike KreftGiovanna ZambrunoArnoud SonnenbergLoss-of-function mutations in the gene encoding the integrin co-activator kindlin-1 cause Kindler syndrome. We report a novel kindlin-1-deficient keratinocyte cell line derived from a Kindler syndrome patient. Despite the expression of kindlin-2, the patient's cells display several hallmarks related to reduced function of β1 integrins, including abnormal cell morphology, cell adhesion, cell spreading, focal adhesion assembly, and cell migration. Defective cell adhesion was aggravated by kindlin-2 depletion, indicating that kindlin-2 can compensate to a certain extent for the loss of kindlin-1. Intriguingly, β1 at the cell-surface was aberrantly glycosylated in the patient's cells, and its expression was considerably reduced, both in cells in vitro and in the patient's epidermis. Reconstitution with wild-type kindlin-1 but not with a β1-binding defective mutant restored the aberrant β1 expression and glycosylation, and normalized cell morphology, adhesion, spreading, and migration. Furthermore, the expression of wild-type kindlin-1, but not of the integrin-binding-defective mutant, increased the stability of integrin-mediated cell-matrix adhesions and enhanced the redistribution of internalized integrins to the cell surface. Thus, these data uncover a role for kindlin-1 in the regulation of integrin trafficking and adhesion turnover.http://europepmc.org/articles/PMC3679067?pdf=render |
| spellingShingle | Coert Margadant Maaike Kreft Giovanna Zambruno Arnoud Sonnenberg Kindlin-1 regulates integrin dynamics and adhesion turnover. PLoS ONE |
| title | Kindlin-1 regulates integrin dynamics and adhesion turnover. |
| title_full | Kindlin-1 regulates integrin dynamics and adhesion turnover. |
| title_fullStr | Kindlin-1 regulates integrin dynamics and adhesion turnover. |
| title_full_unstemmed | Kindlin-1 regulates integrin dynamics and adhesion turnover. |
| title_short | Kindlin-1 regulates integrin dynamics and adhesion turnover. |
| title_sort | kindlin 1 regulates integrin dynamics and adhesion turnover |
| url | http://europepmc.org/articles/PMC3679067?pdf=render |
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