Breakdown of microvilli is a common early event in various types of apoptosis, but its molecular mechanism and implications remain unclear. ERM (ezrin/radixin/moesin) proteins are ubiquitously expressed microvillar proteins that are activated in the cytoplasm, translocate to the plasma membrane, and function as general actin filament/plasma membrane cross-linkers to form microvilli. Immunofluorescence microscopic and biochemical analyses revealed that, at the early phase of Fas ligand (FasL)–induced apoptosis in L cells expressing Fas (LHF), ERM proteins translocate from the plasma membranes of microvilli to the cytoplasm concomitant with dephosphorylation. When the FasL-induced dephosphorylation of ERM proteins was suppressed by calyculin A, a serine/threonine protein phosphatase inhibitor, the cytoplasmic translocation of ERM proteins was blocked. The interleukin-1β–converting enzyme (ICE) protease inhibitors suppressed the dephosphorylation as well as the cytoplasmic translocation of ERM proteins. These findings indicate that during FasL-induced apoptosis, the ICE protease cascade was first activated, and then ERM proteins were dephosphorylated followed by their cytoplasmic translocation, i.e., microvillar breakdown. Next, to examine the subsequent events in microvillar breakdown, we prepared DiO-labeled single-layered plasma membranes with the cytoplasmic surface freely exposed from FasL-treated or nontreated LHF cells. On single-layered plasma membranes from nontreated cells, ERM proteins and actin filaments were densely detected, whereas those from FasL-treated cells were free from ERM proteins or actin filaments. We thus concluded that the cytoplasmic translocation of ERM proteins is responsible for the microvillar breakdown at an early phase of apoptosis and that the depletion of ERM proteins from plasma membranes results in the gross dissociation of actin-based cytoskeleton from plasma membranes. The physiological relevance of this ERM protein–based microvillar breakdown in apoptosis will be discussed.
Skip Nav Destination
Article navigation
3 November 1997
Article|
November 03 1997
ERM (Ezrin/Radixin/Moesin)-based Molecular Mechanism of Microvillar Breakdown at an Early Stage of Apoptosis
Takahisa Kondo,
Takahisa Kondo
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Search for other works by this author on:
Kosei Takeuchi,
Kosei Takeuchi
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Search for other works by this author on:
Yoshinori Doi,
Yoshinori Doi
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Search for other works by this author on:
Shigenobu Yonemura,
Shigenobu Yonemura
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Search for other works by this author on:
Shigekazu Nagata,
Shigekazu Nagata
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Search for other works by this author on:
Shoichiro Tsukita,
Shoichiro Tsukita
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Search for other works by this author on:
Sachiko Tsukita
Sachiko Tsukita
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Search for other works by this author on:
Takahisa Kondo
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Kosei Takeuchi
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Yoshinori Doi
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Shigenobu Yonemura
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Shigekazu Nagata
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Shoichiro Tsukita
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Sachiko Tsukita
*Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan; ‡First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466, Japan; §Department of Cell Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma 630-01, Nara, Japan; ‖Second Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565, Japan; ¶Department of Genetics, Osaka University Medical School, Suita, Osaka 565, Japan; and **College of Medical Technology, Kyoto University, Sakyo-ku, Kyoto 606, Japan
Address all correspondence to Sachiko Tsukita, Ph.D., Department of Cell Biology, Kyoto University Faculty of Medicine, Konoe-Yoshida, Sakyo-ku, Kyoto 606, Japan. Tel.: 81-75-753-4373. Fax: 81-75-753-4660. E-mail: [email protected]
Received:
April 24 1997
Revision Received:
August 13 1997
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1997
J Cell Biol (1997) 139 (3): 749–758.
Article history
Received:
April 24 1997
Revision Received:
August 13 1997
Citation
Takahisa Kondo, Kosei Takeuchi, Yoshinori Doi, Shigenobu Yonemura, Shigekazu Nagata, Shoichiro Tsukita, Sachiko Tsukita; ERM (Ezrin/Radixin/Moesin)-based Molecular Mechanism of Microvillar Breakdown at an Early Stage of Apoptosis . J Cell Biol 3 November 1997; 139 (3): 749–758. doi: https://doi.org/10.1083/jcb.139.3.749
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
Advertisement