Author
John A. Cooper
Other affiliations: Johns Hopkins University, Johns Hopkins University School of Medicine, University of Arizona ...read more
Bio: John A. Cooper is an academic researcher from Washington University in St. Louis. The author has contributed to research in topics: Arp2/3 complex & Actin-binding protein. The author has an hindex of 80, co-authored 200 publications receiving 24891 citations. Previous affiliations of John A. Cooper include Johns Hopkins University & Johns Hopkins University School of Medicine.
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TL;DR: A review briefly summarizes older studies and concentrates on recent studies on the mechanisms of action of cytochalasin and phalloidin.
Abstract: C YTOCHALASINS and phalloidins are two groups of small, naturally occurring organic molecules that bind to actin and alter its polymerization. They have been widely used to study the role of actin in biological processes and as models for actin-binding proteins. Functionally, cytochalasins resemble capping proteins, which block an end of actin filaments, nucleate polymerization, and shorten filaments. No known actin-binding protein stabilizes actin filaments as phalloidin does, but such proteins may have been missed. Cytochalasin and phalloidin have also helped to elucidate fundamental aspects of actin polymerization. This review briefly summarizes older studies and concentrates on recent v~rk on the mechanisms of action of cytochalasin and phalloidin.
1,978 citations
TL;DR: Comparisons of quantitative measurements of reactions in live cells with computer simulations of mathematical models will help generate meaningful insights and present a summary of the key questions in the field.
Abstract: The protein actin forms filaments that provide cells with mechanical support and driving forces for movement. Actin contributes to biological processes such as sensing environmental forces, internalizing membrane vesicles, moving over surfaces, and dividing the cell in two. These cellular activities are complex; they depend on interactions of actin monomers and filaments with numerous other proteins. Here, we present a summary of the key questions in the field and suggest how those questions might be answered. Understanding actin-based biological phenomena will depend on identifying the participating molecules and defining their molecular mechanisms. Comparisons of quantitative measurements of reactions in live cells with computer simulations of mathematical models will also help generate meaningful insights.
1,765 citations
TL;DR: The nucleotide sequence of a contiguous 2,181,032 base pairs in the central gene cluster of chromosome III is completed, and comparison with the public sequence databases reveals similarities to previously known genes for about one gene in three.
Abstract: As part of our effort to sequence the 100-megabase (Mb) genome of the nematode Caenorhabditis elegans, we have completed the nucleotide sequence of a contiguous 2,181,032 base pairs in the central gene cluster of chromosome III. Analysis of the finished sequence has indicated an average density of about one gene per five kilobases; comparison with the public sequence databases reveals similarities to previously known genes for about one gene in three. In addition, the genomic sequence contains several intriguing features, including putative gene duplications and a variety of other repeats with potential evolutionary implications.
1,612 citations
TL;DR: The present study focuses on the development of binding proteins that bind to the sides of ACTIN FILAMENTS and their applications in the context of nanofiltration.
Abstract: PERSPECTIVES AND SUMMARY 988 INTRODUCTION 988 THE ACTIN MOLECULE 989 MECHANISM OF POL YMERIZA TION , , 994 MECHANICAL PROPERTIES , 1004 ACTIN MONOMER BINDING PROTEINS 1006 CAPPING PROTEINS , 1011 LOW-MOLECULAR-WEIGHT SEVERING PROTEINS 1018 PROTEINS THAT BIND TO THE SIDES OF ACTIN FILAMENTS 1019 MEMBRANE ATTACHMENT PROTEINS 1026 FUTURE RESEARCH 1029
1,465 citations
TL;DR: It is concluded that Ena/VASP regulates cell motility by controlling the geometry of actin filament networks within lamellipodia.
850 citations
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TL;DR: A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.
Abstract: The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.
70,111 citations
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
22,269 citations
TL;DR: Molecular genetic and biochemical studies described here suggest that, as in the case of growth factor receptors of higher eukaryotic cells, Ire1p oligomerizes in response to the accumulation of unfolded proteins in the ER and is phosphorylated in trans by otherIre1p molecules as a result of oligomerization.
Abstract: The transmembrane kinase Ire1p is required for activation of the unfolded protein response (UPR), the increase in transcription of genes encoding endoplasmic reticulum (ER) resident proteins that occurs in response to the accumulation of unfolded proteins in the ER. Ire1p spans the ER membrane (or the nuclear membrane with which the ER is continuous), with its kinase domain localized in the cytoplasm or in the nucleus. Consistent with this arrangement, it has been proposed that Ire1p senses the accumulation of unfolded proteins in the ER and transmits the signal across the membrane toward the transcription machinery, possibly by phosphorylating downstream components of the UPR pathway. Molecular genetic and biochemical studies described here suggest that, as in the case of growth factor receptors of higher eukaryotic cells, Ire1p oligomerizes in response to the accumulation of unfolded proteins in the ER and is phosphorylated in trans by other Ire1p molecules as a result of oligomerization. In addition to its kinase domain, a C-terminal tail domain of Ire1p is required for induction of the UPR. The role of the tail is probably to bind other proteins that transmit the unfolded protein signal to the nucleus.
12,185 citations
TL;DR: An approach for genome analysis based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence of the genome from the bacterium Haemophilus influenzae Rd.
Abstract: An approach for genome analysis based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence (1,830,137 base pairs) of the genome from the bacterium Haemophilus influenzae Rd. This approach eliminates the need for initial mapping efforts and is therefore applicable to the vast array of microbial species for which genome maps are unavailable. The H. influenzae Rd genome sequence (Genome Sequence DataBase accession number L42023) represents the only complete genome sequence from a free-living organism.
5,944 citations
TL;DR: It is reported here that cdc42, another member of the rho family, triggers the formation of a third type of actin-based structure found at the cell periphery, filopodia, in addition to stress fibers, and rho controls the assembly of focal adhesion complexes.
4,440 citations