Abstract：
:In fibroblasts, platelet-derived growth factor receptor alpha (PDGFRα) is upregulated during growth arrest and compartmentalized to the primary cilium. PDGF-AA mediated activation of the dimerized ciliary receptor produces a phosphorylation cascade through the PI3K-AKT and MEK1/2-ERK1/2 pathways leading to the activation of the Na(+)/H(+) exchanger, NHE1, cytoplasmic alkalinization and actin nucleation at the lamellipodium that supports directional cell migration. We here show that AKT and MEK1/2-ERK1/2-p90(RSK) inhibition reduced PDGF-AA-induced cell migration by distinct mechanisms: AKT inhibition reduced NHE1 activity by blocking the translocation of NHE1 to the cell membrane. MEK1/2 inhibition did not affect NHE1 activity but influenced NHE1 localization, causing NHE1 to localize discontinuously in patches along the plasma membrane, rather than preferentially at the lamellipodium. We also provide direct evidence of NHE1 translocation through the cytoplasm to the leading edge. In conclusion, signals initiated at the primary cilium through the PDGFRαα cascade reorganize the cytoskeleton to regulate cell migration differentially through the AKT and the MEK1/2-ERK1/2-p90(RSK) pathways. The AKT pathway is necessary for initiation of NHE1 translocation, presumably in vesicles, to the leading edge and for its activation. In contrast, the MEK1/2-ERK1/2-p90(RSK) pathway controls the spatial organization of NHE1 translocation and incorporation, and therefore specifies the direction of the leading edge formation.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Clement DL,Mally S,Stock C,Lethan M,Satir P,Schwab A,Pedersen SF,Christensen STdoi
10.1242/jcs.116426subject
Has Abstractpub_date
2013-02-15 00:00:00pages
953-65issue
Pt 4eissn
0021-9533issn
1477-9137pii
jcs.116426journal_volume
126pub_type
杂志文章abstract：:The notion that cell shape and spreading can regulate cell proliferation has evolved over several years, but only recently has this been linked to forces from within and upon the cell. This emerging area of mechanical signaling is proving to be wide-spread and important for all cell types. The microenvironment that su...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.067009
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abstract：:The inclusion of lymphocytes in high endothelial venules and their migration to the lymph nodes are critical steps in the immune response. Cell migration is regulated by the actin cytoskeleton and myosins. Myo1e is a long-tailed class I myosin and is highly expressed in B cells, which have not been studied in the cont...
journal_title：Journal of cell science
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doi：10.1242/jcs.235275
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abstract：:Actin functions in a multitude of cellular processes owing to its ability to polymerize into filaments, which can be further organized into higher-order structures by an array of actin-binding and regulatory proteins. Therefore, research on actin and actin-related functions relies on the visualization of actin structu...
journal_title：Journal of cell science
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journal_title：Journal of cell science
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doi：10.1242/jcs.02674
更新日期：2005-12-01 00:00:00
abstract：:Hepatocyte growth factor (HGF)/scatter factor modulates the motility of HT29 colon carcinoma cells in vitro by inducing morphological changes that depend on the type of extra-cellular matrix (ECM) ligand; HGF-induced scattering of HT29 cells is observed if cells are grown on plastic coated with serum proteins but not ...
journal_title：Journal of cell science
pub_type： 杂志文章
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journal_title：Journal of cell science
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doi：10.1242/jcs.03418
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
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abstract：:An electron microscopic investigation of the events associated with meiosis in Lilium has revealed a number of changes in both the organellar population and the other cytoplasmic components. Ribosome numbers decrease significantly in early prophase and are later replenished in the tetrads, a process most likely involv...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
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pub_type： 杂志文章
doi：10.1242/jcs.117564
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章,评审
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更新日期：2016-03-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.236505
更新日期：2019-11-14 00:00:00
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doi：10.1242/jcs.210419
更新日期：2018-01-08 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-05-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.110361
更新日期：2013-01-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-06-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
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journal_title：Journal of cell science
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
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journal_title：Journal of cell science
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-02-01 00:00:00
