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© The Rockefeller University Press, 0021-9525/2000//573 $5.00
The Journal of Cell Biology, Volume 151, Number 3, , 2000 573-586

Subcellular Distribution of Envoplakin and Periplakin

Teresa DiColandrea^a, Tadashi Karashima^a, Arto Määttä^a, and Fiona M. Watt^a

^a Keratinocyte Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, England
Imperial Cancer Research Fund, P.O. Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, England.44 20 7269 3528; Fax: 44 20 7269 3078; E-mail: watt@icrf

Envoplakin and periplakin are two plakins that are precursors of the epidermal cornified envelope. We studied their distribution and interactions by transfection of primary human keratinocytes and other cells. Full-length periplakin localized to desmosomes, the interdesmosomal plasma membrane and intermediate filaments. Full length envoplakin also localized to desmosomes, but mainly accumulated in nuclear and cytoplasmic aggregates with associated intermediate filaments. The envoplakin rod domain was required for aggregation and the periplakin rod domain was necessary and sufficient to redistribute envoplakin to desmosomes and the cytoskeleton, confirming earlier predictions that the proteins can heterodimerize. The linker domain of each protein was required for intermediate filament association. Like the NH₂ terminus of desmoplakin, that of periplakin localized to desmosomes; however, in addition, the periplakin NH₂ terminus accumulated at cell surface microvilli in association with cortical actin. Endogenous periplakin was redistributed from microvilli when keratinocytes were treated with the actin disrupting drug Latrunculin B. We propose that whereas envoplakin and periplakin can localize independently to desmosomes, the distribution of envoplakin at the interdesmosomal plasma membrane depends on heterodimerization with periplakin and that the NH₂ terminus of periplakin therefore plays a key role in forming the scaffold on which the cornified envelope is assembled.

Key Words: envoplakin • periplakin • desmosomes • cornified envelope • keratinocytes

© 2000 The Rockefeller University Press

T. Karashima is on leave from Department of Dermatology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830, Japan.

Abbreviations used in this paper: FAD, Ham's F12 medium + adenine+ DME; FGS, fish skin gelatin; HA, hemagglutinin; HICE, hydrocortisone + insulin + cholera toxin + EGF; KSFM, keratinocyte serum-free medium.

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