Receptor-Mediated Binding and Internalization of Toxins and Hormones

373 Pages·1981·42.835 MB·English

by  John Middlebrook (Eds.)

Academic Press Rapid Manuscript Reproduction
THE PROCEEDINGS OF A SYMPOSIUM BASED ON THE
CONFERENCE ON RECEPTOR-MEDIATED BINDING AND
INTERNALIZATION OF TOXINS AND HORMONES, HELD IN
FREDERICK, MARYLAND, ON MARCH 24-26, 1980, SPONSORED
BY THE U.S. ARMY MEDICAL RESEARCH INSTITUTE FOR
INFECTIOUS DISEASES.
RECEPTOR-MEDIATED BINDING
AND INTERNALIZATION
OF TOXINS AND HORMONES
Edited by
JOHN L. MIDDLEBROOK
Pathology Division
U.S. Army Medical Research Institute of Infectious Diseases
Fort Detrick, Frederick, Maryland
LEONARD D. KOHN
Laboratory of Biochemical Pharmacology
National Institutes of Arthritis and Metabolic Digestive Disorders
National Institutes of Health
Bethesda, Maryland
ACADEMIC PRESS 1981
A Subsidiary of Harcourt Brace Jovanovich, Publishers
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COPYRIGHT © 1981, BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED.
NO PART OF THIS PUBLICATION MAY BE REPRODUCED OR
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ACADEMIC PRESS, INC.
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United Kingdom Edition published by
ACADEMIC PRESS, INC. (LONDON) LTD.
24/28 Oval Road, London NW1 7DX
Library of Congress Cataloging in Publication Data
Main entry under title:
Receptor-mediated binding and internalization of toxins
and hormones.
1. Hormone receptors—Congresses. 2. Toxins—Receptors
—Congresses. 3. Endocytosis—Congresses. 4. Binding
sites (Biochemistry)—Congresses.
1. Middlebrook, John L. II. Kohn, Leonard D. III. United
States Army Medical Research Institute of Infectious
Diseases. [DNLM: 1. Binding sites—Congresses.
2. Hormones—Physiology—Congresses. 3. Toxins—
Metabolism—Congresses. 4. Receptors, Hormones—
Physiology—Congresses. QW 630 R295 1980]
QP571.7.R43 ι6 12'.015 81-3595
ISBN 0-12-494850-2 AACR2
PRINTED IN THE UNITED STATES OF AMERICA
81 82 83 84 9 8 7 6 5 4 3 21
CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors' contributions begin.
Abraham Amsterdam (283), Endocrinology and Reproduction Research Branch,
National Institute of Child Health and Human Development, National Insti-
tutes of Health, Bethesda, Maryland 20205
Richard G. W. Anderson (1), Departments of Cell Biology and Molecular Ge-
netics, University of Texas Health Science Center at Dallas, Dallas, Texas
75235
Mario Ascoli (271), Division of Endocrinology, Vanderbilt University School of
Medicine, Nashville, Tennessee 37232
Joffre B. Baker (259), Department of Biochemistry, University of Kansas, Law-
rence, Kansas
John J. M. Bergeron (197), Departments of Anatomy and Medicine, McGill Uni-
versity, Montreal, H3A2B2 Canada
Paulos Berhanu (181), Division of Pharmacology and Therapeutics, University of
Calgary, Calgary, Alberta, Canada T2N IN4
H. Blythman (351), Department of Immunology, Center de Recherches Clin.
Midy, Rue de Prof Joseph Blayac, 34082 Montpellier Cedex, France
Michael S. Brown (1), Departments of Cell Biology and Molecular Genetics, Uni-
versity of Texas Health Science Center at Dallas, Dallas, Texas 75235
Graham Carpenter (163), Department of Biochemistry, Vanderbilt University
School of Medicine, Nashville, Tennessee 37232
Jean-Louis Carpentier (251), Institute of Histology and Embryology, University
of Geneva Medical School, Geneva, Switzerland
D. Carrière (351), Department of Immunology, Center de Recherches Clin. Midy,
Rue de Prof. Joseph Blayac, 34082 Montpellier Cedex, France
P. Casellas (351), Department of Immunology, Center de Recherches Clin. Midy,
Rue de Prof Joseph Blayac, 34082 Montpellier Cedex, France
Kevin J. Catt (283), Endocrinology and Reproduction Research Branch, National
Institute of Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland 20205
Daniel Chin (53), Department of Biology, University of California at San Diego,
La Jolla, California 92093
Stanley Cohen (163), Department of Biochemistry, Veterans Administration Hos-
pital, Nashville, Tennessee
R. John Collier (311), Department of Microbiology, University of California at
Los Angeles, Los Angeles, California 90024
IX
χ Contributors
Dennis D. Cunningham (259), Department of Microbiology, California College
of Medicine, University of California, Irvine, California
Rebecca B. Dorland (15, 65), Pathology Division, U.S. Army Medical Research
Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21701
Maria L. Dufau (283), Endocrinology and Reproduction Research Branch, Na-
tional Institute of Child Health and Human Development, National Institutes
of Health, Bethesda, Maryland 20205
Christian de Duve (363), International Institute of Cellular and Molecular Pa-
thology, Brussels, Belgium
James T. Forbes (339), Department of Medicine, Vanderbilt University School of
Medicine, Nashville, Tennessee 37232
C. Fred Fox (149), Molecular Biology Institute, University of California at Los
Angeles, Los Angeles, California 90024
D. Michael Gill (113), Department of Molecular Biology and Microbiology, Tufts
University School of Medicine, Boston, Massachusetts 02111
D. Gary Gilliland (311), Department of Microbiology, University of California at
Los Angeles, Los Angeles, California 90024
Ira D. Goldfine (233), Cell Biology Laboratory, Mount Zion Hospital and Medi-
cal Center, San Francisco, California 94120
Joseph L. Goldstein (1), Departments of Cell Biology and Molecular Genetics,
University of Texas Health Science Center at Dallas, Dallas, Texas 75235
Nicholas Gonatas (123), Department of Pathology, Johnson Pavilion, University
of Pennsylvania, Philadelphia, Pennsylvania 19104
Jacqueline Gonatas (123), Department of Pathology, Johnson Pavilion, Univer-
sity of Pennsylvania, Philadelphia, Pennsylvania 19104
Phillip Gorden (251), Diabetes Branch, National Institutes of Arthritis, Metabo-
lism, and Digestive Diseases, National Institutes of Health, Bethesda, Mary-
land 20014
Denis Gospodarowicz (219), Cancer Research Institute, University of California
Medical Center, San Francisco, California 94143
P. Gros (351), Department of Immunology, Center de Recherches Clin. Midy, Rue
de Prof. Joseph Blayac, 34082 Montpellier Cedex, France
Wyrta Heagy (329), Section on Biophysical Chemistry, Laboratory of Neurochem-
istry, National Institute of Mental Health, Bethesda, Maryland 20014
Randy Hock (181), Division of Pharmacology and Therapeutics, University of
Calgary, Calgary, Alberta, Canada T2N 1N4
Morley D. Hollenberg (181), Division of Pharmacology and Therapeutics, Uni-
versity of Calgary, Calgary, Alberta, Canada T2N 1N4
James A. Hope (113), Department of Molecular Biology and Microbiology, Tufts
University School of Medicine, Boston, Massachusetts 02111
Gary T. Hradek (233), Cell Biology Section, Veterans Administration Hospital,
San Francisco, California
Deborah S.Jacobs (113), Harvard University, Cambridge, Massachusetts 02138
F. K. Jansen (351), Department of Immunology, Center de Recherches Clin. Midy,
Rue de Prof. Joseph Blayac, 34082 Montpellier Cedex, France
Contributors χι
Albert L. Jones (233), Cell Biology Section, Veterans Administrations Hospital,
San Francisco, California
Gerald T. Keusch (95), Department of Medicine, Tufts University School of Med-
icine, Boston, Massachusetts 02111
Lloyd King, Jr. (163), Division of Dermatology, Department of Medicine, Vet-
erans Administration Hospital, Nashville, Tennessee
Michael Knecht (283), Endocrinology and Reproduction Research Branch, Na-
tional Institute of Child Health and Human Development, National Institutes
of Health, Bethesda, Maryland 20205
Barbara M. Kriz (233), Cell Biology Laboratory, Mount Zion Hospital and Medi-
cal Center, San Francisco, California 94120
Stephen H. Leppla (65), Pathology Division, U.S. Army Medical Research Insti-
tute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21701
Peter S. Linsley (149), Molecular Biology Institute, University of California, Los
Angeles, California 90024
David A. Low (259), Department of Microbiology, California College of Medi-
cine, University of California, Irvine, California
Josef Mannhalter (311), Department of Microbiology, University of California at
Los Angeles, Los Angeles, California 90024
Roberta Meren (113), Department of Molecular Biology and Microbiology, Tufts
University School of Medicine, Boston, Massachusetts 02111
John L. Middlebrook (15), Pathology Division, U.S. Army Medical Research
Institute of Infectious Diseases, Fort Detrick, Federick, Maryland 21701
Takashi Mommoi (123), Department of Pathobiochemical Cell Research, Univer-
sity of Tokyo, Tokyo, Japan
Michael R. Moynihan (31), Department of Biology, Harvard University, Cam-
bridge, Massachusetts 02138
Gary J. Murray (329), Section on Biophysical Chemistry, Laboratory of Neuro-
chemistry, National Institute of Mental Health, National Institutes of Health,
Bethesda, Maryland 20014
Zvi Naor (283), Endocrinology and Reproduction Branch, National Institute of
Child Health and Human Development, National Institutes of Health, Be-
thesda, Maryland 20205
Ebba Nero (181), Division of Pharmacology and Therapeutics, University of Cal-
gary, Calgary, Alberta, Canada T2N 1N4
Elizabeth F. Neufeld (11), Genetics and Biochemistry Branch, National Institute
of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health,
Bethesda, Maryland 20205
David M. Neville, Jr. (329), Section on Biophysical Chemistry, Laboratory of
Neurochemistry, National Institute of Mental Health, National Institutes of
Health, National Institutes of Health, Bethesda, Maryland 20014
Thomas N. Oeltmann (339), Department of Medicine, Vanderbilt University
School of Medicine, Nashville, Tennessee 37232
Sjur Olsnes (81), Department of Biochemistry, Norsk Hydro's Institute for Cancer
Research, Montebello, Oslo 3, Norway
xii Contributors
Lelio Orci (251), Institute of Histology and Embryology, University of Geneva
Medical School, Geneva, Switzerland
F. Paolucci (351), Department of Immunology, Center de Recherches Clin. Midy,
Rue de Prof. Joseph Blayac, 34082 Montpellier Cedex, France
A. M. Pappenheimer, Jr. (31), Department of Biology, Harvard University
Cambridge, Massachusetts 02138
Ira H. Pastan (135), Laboratory of Molecular Biology, Division of Cancer Biology
and Diagnosis, National Cancer Institute, National Institutes of Health, Be-
thesda, Maryland 20014
B. Pau (351), Department of Immunology, Center de Recherches Clin. Midy, Rue
de Prof. Joseph Blayac, 34082 Montpellier Cedex, France
P. Poncelet (351), Department of Immunology, Center de Recherches Clin. Midy,
Rue de Prof. Joseph Blayac, 34082 Montpellier Cedex, France
Barry I. Posner (197), Departments of Anatomy and Medicine, McGill Univer-
sity, Montreal, H3A2B2 Canada
Richard Renston (233), Cell Biology Section, Veterans Administration Hospital,
San Francisco, California
G. Richer (351), Department of Immunology, Center de Recherches Clin. Midy,
Rue de Prof. Joseph Blayac, 34082 Montpellier Cedex, France
Kirsten Sandvig (81), Department of Biochemistry, Norsk Hydro's Institute for
Cancer Research, Montebello, Oslo 3, Norway
Randy W. Scott (259), Department of Biochemistry, University of Kansas,
Lawrence, Kansas
Melvin I. Simon (53), Department of Biology, University of California at San
Diego, La Jolla, California 92093
Anna Stieber, (123), Department of Pathology, University of Pennsylvania, Phil-
adelphia, Pennsylvania 19104
H. Vidal (351), Department of Immunology, Center de Recherches Clin. Midy,
Rue de Prof. Joseph Blayac, 34082 Montpellier Cedex, France
Mark C. Willingham (135), Laboratory of Molecular Biology, Division of Cancer
Biology and Diagnosis, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland 20014
Κ. Y. Wong (233), Cell Biology Laboratory, Mount Zion Hospital and Medical
Center, San Francisco, California 94120
Richard J. Youle (329), Section on Biophysical Chemistry, Laboratory of Neuro-
chemistry, National Institute of Mental Health, National Institutes of Health,
Bethesda, Maryland 20014
PREFACE
The purpose of the conference on which this volume is based was to
explore relationships between hormones and toxins, specifically, receptor-
mediated internalization of toxins and hormones and the role of this inter-
nalization in message transmission and biodegradatory processes.
Interest in the structure of toxins and the mechanisms by which they
elicit their effects on cells has long intrigued scientists concerned with hu-
man disease states, and has also stemmed from the recognition that toxins
probe normal cell regulation systems by virtue of their ability to modulate
normal physiologic and biochemical functions. Thus, work in the diphthe-
ria toxin field has led to increased understanding of protein biosynthesis,
and studies of cholera toxin have improved our understanding of the
mechanisms by which the adenylate cyclase system effects its message role.
Studies of both cholera and diphtheria toxin have led to a resurgence of
interest in the role of NAD and ADP-ribosylation as regulators of key func-
tional processes of the cell.
Perhaps the most recent surge of interest in toxins has come from obser-
vations that toxins are related to hormones and neurotropic agents, which
regulate the normal physiology of the cell, and organism and to interferon,
which protects cells from viral attack. Thus cholera toxin is now used as a
"biologic blocker" to confirm interferon action and has a sequence homol-
ogy with interferon. Tetanus toxin is now established as a specific marker
for neural cells and has effects on membrane potential change and calcium
flux elicited by hormones such as epinephrine. The sympathetic overactiv-
ity syndrome seen in severe cases of tetanus is identical to thyroid storm.
Bungarotoxin and the acetylcholine receptor are almost synonymous
terms. Pituitary glycoprotein hormones such as thy to tropin have sequence
analogies with cholera toxin; analogies in receptor structure have been pos-
tulated; and relationships between second-message generation at the
adenylate cyclase level are being questioned. Scorpion and other toxins are
being used "diagnostically" to evaluate the effects of hormones and neuro-
tropic agents on ion permeability across cell membranes, in particular so-
dium-calcium permeability properties which affect the cell by altering
calmodulin-regulated functions.
In Section I, two internalization models which could act as biochemical
reference points are summarized and reviewed. In Section II, internaliza-
tion mechanisms are explored in detail, and internalization of several rep-
resentative toxins (diphtheria, cholera, ricin, abrin, Pseudomonas) and hor-
Xlll
XIV Preface
mones or analogous bioactive ligands (insulin, chorionic gonadotrophin,
growth factors) is presented. It will be evident to the reader, as it was to the
conference participants, that studies and approaches within both fields are
yielding analogous data and concerns, and that close coordination of the
fields is now a necessity.
Perhaps the most illustrative point emphasizing the fact that this concern
is of immediate relevance to the entire biomedical community are experi-
ments in which hybrid hormones and toxins are formed and targeted to
specific cells by taking advantage of the binding properties of one and the
effect on cell processing of the other. This approach, covered in Section
III, is already reality in the creation of new biologic agents which may tar-
get to a tumor cell and then kill it: those which target to a cell needing a
growth stimulus to reestablish its functional vigor, or which target to a cell
to reverse a pathologic state. Section IV is the (edited) summation address
given by Dr. Christian deDuve.
This first conference was a success not only because of the efforts its
participants but also because of the strong support provided by the staff of
the United States Army Medical Research Institute, Fort Detrick, Fred-
erick, Maryland. In particular, we would like to thank Martin J. Hilt, Larry
Campbell, Mary Culler, Dennis Leatherman, Phebe W. Summers, Roy
Culler, and Rebecca Dorland for their valuable assistance in various aspects
of running the conference and compiling this volume.
John L. Middlebrook
Leonard D. Kohn
PICTORIAL ILLUSTRATION OF THE RECEPTOR-MEDIATED
ENDOCYTOSIS OF LOW DENSITY LIPOPROTEIN
VIA COATED REGIONS OF MEMBRANE
Richard G.W. Anderson, Joseph L. Goldstein, and
Michael S. Brown
Departments of Cell Biology and Molecular Genetics
University of Texas Health Science Center at Dallas
5323 Harry Hines Blvd.
Dallas, Texas 75235
INTRODUCTION
Receptor-mediated endocytosis has been described for a
wide variety of extracellular ligands, including transport
proteins (1,2), protein hormones (3,4), asialoglycoproteins
(5), modified plasma proteins (6), lysosomal enzymes (7),
viruses (8), and certain toxins (9). In each case, the
binding of the molecule to a cell surface receptor is the
first in a series of events that include: a) invagination
of the section of membrane containing the bound ligand,
b) formation of endocytic vesicles, and c) delivery of
vesicular contents to a specific intracellular compartment.
Whereas ligand selectivity during receptor-mediated
endocytosis is a function of the cell surface membrane-
receptor, the efficiency of the uptake process is a function
of the location of the receptor in specialized regions of
the cell surface that are adapted to the rapid formation of
endocytic vesicles (reviewed in réf. 1).
Two modes of membrane internalization are likely to
account for most endocytic events:
1. The invagination and formation of cytoplasmic
vesicles from 0.1-0.2 ym segments of surface membrane that
are distinguished by the presence of a cytoplasmic coat
RECEPTOR-MEDIATED BINDING AND Copyright © 1981 by Academic Press, Inc.
INTERNALIZATION OF TOXINS AND HORMONES ^ AU ri8hts of reproduction in any form reserved.
ISBN 0-12-494850-2