Do Epiplakin connect with tight junctions?

• Project/Area Number: 25860959
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Oita University
• Principal Investigator: ISHIKAWA Kazushi 大分大学, 医学部, 助教 (80600452)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: エピプラキン / 自己免疫性水疱症 / 自己抗原 / プラキンファミリー分子 / 表皮下水疱症 / タイトジャンクション / 中間径フィラメント / 自己免疫性表皮水疱症 / 分子生物学

Outline of Final Research Achievements

To study the function of EPPK, we developed EPPK knock-down (KD) and EPPK-overexpressing HeLa cells and analyzed cellular phenotypes and motility. Cellular motility of EPPK-KD cells was significantly elevated, but that of EPPK-overexpressing cells was obviously depressed. Many spike-like projections were observed on EPPK-KD cells, with fewer such structures on overexpressing cells. By contrast, in EPPK-KD cells, expression of E-cadherin was unchanged but vimentin fibers were thinner and sparser than in controls, and they were more concentrated at the peri-nucleus, as observed in migrating keratinocytes at wound edges in EPPK-/- mice. In Matrigel 3-D cultures, EPPK co-localized on the outer surface of cell clusters with zonula occludens-1 (ZO-1), a marker of tight junctions. Our results suggest that EPPK is associated with the machinery for cellular motility and contributes to tissue architecture via the rearrangement of intermediate filaments.

Research Products

• [Journal Article] Association between HLA-DRB1*0405, -DQB1*0401 and -DQA1*0303 alleles and lamotrigine-induced cutaneous adverse drug reactions. A pilot case-control study from Japan (2015)
  • Author(s): Ito A, Shimada H, Ishikawa K, Takeo N, Hatano Y, Katagiri K, Kohno K, Araki Y, Terao T, Kojima H, Terao C, Eshima N, Fujiwara S
  • Journal Title: Journal of Affected Disorders Volume: 179 Pages: 47-50
  • DOI: 10.1016/j.jad.2015.03.018
  • Peer Reviewed
• [Journal Article] A case of concurrent pemphigoid vegetans and pemphigus vegetans resolving without oral corticosteroid (2014)
  • Author(s): Hatano Y, Ishikawa K, Koga H, Ishii N, Hashimoto T, Takeo N, Shimada H, Sakai T, Okamoto O, Fujiwara S
  • Journal Title: British Journal of Dermatology Volume: 179 Issue: 5 Pages: 47-50
  • DOI: 10.1111/bjd.12802
  • Peer Reviewed
• [Journal Article] Epiplakin modifies the motility of the HeLa cells and accumulates at the outer surfaces of 3-D cell clusters. (2013)
  • Author(s): Shimada H, Nambu-Niibori A, Wilson-Morifuji M, Mizuguchi S, Araki N, Sumiyoshi H, Sato M, Mezaki Y, Senoo H, Ishikawa K, Hatano Y, Okamoto O, Fujiwara S
  • Journal Title: J Dermatol Volume: 40 Issue: 4 Pages: 249-58
  • DOI: 10.1111/1346-8138.12076
  • Peer Reviewed
• [Journal Article] Increased fragility, impaired differentiation, and acceleration of migration of corneal epithelium of epiplakin-null mice. (2013)
  • Author(s): Kokado M, Okada Y, Goto M, Ishikawa K, Miyamoto T, Yamanaka O, Fujiwara S, Saika S
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 54 Issue: 5 Pages: 3780-9
  • DOI: 10.1167/iovs.12-11077
  • Peer Reviewed