Abstract
Proper control of cell cycle progression and barrier function are essential processes to the maintenance of epithelial cell homeostasis. The contribution of tight junction proteins to barrier function is well established, whereas their contribution to cell cycle control is only beginning to be understood. Centrosomes are the principal microtubule organizing centers in eukaryotic cells and centrosome duplication and separation are linked to the cell cycle and mitotic entry. Here we demonstrate that occludin localizes with centrosomes in Madin-Darby canine kidney cells. Immunocytochemistry and biochemical fractionation studies reveal occludin localizes with centrosomes during interphase and occludin Ser-490 phosphorylation at centrosomes increases with mitotic entry. Stable expression of aspartic acid phosphomimetic (S490D) results in centrosomal localization of occludin and increases cell numbers. Furthermore, we provide evidence that occludin regulates centrosome separation and mitotic entry as the nonphosphorylatable alanine mutation (S490A) impedes centrosome separation, delays mitotic entry, and reduces proliferation. Collectively, these studies demonstrate a novel location and function for occludin in centrosome separation and mitosis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 30847-30858 |
| Number of pages | 12 |
| Journal | Journal of Biological Chemistry |
| Volume | 286 |
| Issue number | 35 |
| DOIs | |
| State | Published - Sep 2 2011 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Cell Biology
- Molecular Biology
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Occludin localizes to centrosomes and modifies mitotic entry. / Runkle, E. Aaron; Sundstrom, Jeffrey; Runkle, Kristin B.; Liu, Xuwen; Antonetti, David A.
In: Journal of Biological Chemistry, Vol. 286, No. 35, 02.09.2011, p. 30847-30858.Research output: Contribution to journal › Article
TY - JOUR
T1 - Occludin localizes to centrosomes and modifies mitotic entry
AU - Runkle, E. Aaron
AU - Sundstrom, Jeffrey
AU - Runkle, Kristin B.
AU - Liu, Xuwen
AU - Antonetti, David A.
PY - 2011/9/2
Y1 - 2011/9/2
N2 - Proper control of cell cycle progression and barrier function are essential processes to the maintenance of epithelial cell homeostasis. The contribution of tight junction proteins to barrier function is well established, whereas their contribution to cell cycle control is only beginning to be understood. Centrosomes are the principal microtubule organizing centers in eukaryotic cells and centrosome duplication and separation are linked to the cell cycle and mitotic entry. Here we demonstrate that occludin localizes with centrosomes in Madin-Darby canine kidney cells. Immunocytochemistry and biochemical fractionation studies reveal occludin localizes with centrosomes during interphase and occludin Ser-490 phosphorylation at centrosomes increases with mitotic entry. Stable expression of aspartic acid phosphomimetic (S490D) results in centrosomal localization of occludin and increases cell numbers. Furthermore, we provide evidence that occludin regulates centrosome separation and mitotic entry as the nonphosphorylatable alanine mutation (S490A) impedes centrosome separation, delays mitotic entry, and reduces proliferation. Collectively, these studies demonstrate a novel location and function for occludin in centrosome separation and mitosis.
AB - Proper control of cell cycle progression and barrier function are essential processes to the maintenance of epithelial cell homeostasis. The contribution of tight junction proteins to barrier function is well established, whereas their contribution to cell cycle control is only beginning to be understood. Centrosomes are the principal microtubule organizing centers in eukaryotic cells and centrosome duplication and separation are linked to the cell cycle and mitotic entry. Here we demonstrate that occludin localizes with centrosomes in Madin-Darby canine kidney cells. Immunocytochemistry and biochemical fractionation studies reveal occludin localizes with centrosomes during interphase and occludin Ser-490 phosphorylation at centrosomes increases with mitotic entry. Stable expression of aspartic acid phosphomimetic (S490D) results in centrosomal localization of occludin and increases cell numbers. Furthermore, we provide evidence that occludin regulates centrosome separation and mitotic entry as the nonphosphorylatable alanine mutation (S490A) impedes centrosome separation, delays mitotic entry, and reduces proliferation. Collectively, these studies demonstrate a novel location and function for occludin in centrosome separation and mitosis.
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UR - http://www.scopus.com/inward/citedby.url?scp=80052207922&partnerID=8YFLogxK
U2 - 10.1074/jbc.M111.262857
DO - 10.1074/jbc.M111.262857
M3 - Article
VL - 286
SP - 30847
EP - 30858
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 35
ER -