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Book ; Conference proceedings: Molecular approaches to developmental biology

Firtel, Richard A.

proceed. of the Dupont-Genentech UCLA Symposium [Molecular Approaches to Developmental Biology] held at Keystone, Colo., March 30 - April 6, 1986

(UCLA Symposia on Molecular and Cellular Biology ; N.s.,51)

1987

Institution	Symposium Molecular Approaches to Developmental Biology
Author's details	ed.: Richard A. Firtel
Series title	UCLA Symposia on Molecular and Cellular Biology ; N.s.,51
Collection
Keywords	Embryology / congresses ; Molecular Biology / congresses ; Molekularbiologie ; Entwicklungsbiologie
Subject	Molekulare Biologie
Size	XXIV, 695 S. : Ill., graph. Darst.
Publisher	Liss
Publishing place	New York
Publishing country	United States
Document type	Book ; Conference proceedings
HBZ-ID	HT003000448
ISBN	0-8451-2650-4 ; 978-0-8451-2650-9
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Phosphodiesterase PdeD, dynacortin, and a Kelch repeat-containing protein are direct GSK3 substrates in Dictyostelium that contribute to chemotaxis towards cAMP.

Baumgardner, Kimberly / Lin, Connie / Firtel, Richard A / Lacal, Jesus

Environmental microbiology

2018 Volume 20, Issue 5, Page(s) 1888–1903

Abstract: The migration of cells according to a diffusible chemical signal in their environment is called chemotaxis, and the slime mold Dictyostelium discoideum is widely used for the study of eukaryotic chemotaxis. Dictyostelium must sense chemicals, such as ... ...

Abstract	The migration of cells according to a diffusible chemical signal in their environment is called chemotaxis, and the slime mold Dictyostelium discoideum is widely used for the study of eukaryotic chemotaxis. Dictyostelium must sense chemicals, such as cAMP, secreted during starvation to move towards the sources of the signal. Previous work demonstrated that the gskA gene encodes the Dictyostelium homologue of glycogen synthase kinase 3 (GSK3), a highly conserved serine/threonine kinase, which plays a major role in the regulation of Dictyostelium chemotaxis. Cells lacking the GskA substrates Daydreamer and GflB exhibited chemotaxis defects less severe than those exhibited by gskA
MeSH term(s)	8-Bromo Cyclic Adenosine Monophosphate/analogs & derivatives ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Chemotaxis/physiology ; Cyclic AMP/metabolism ; Dictyostelium/enzymology ; Gene Expression Regulation ; Glycogen Synthase Kinase 3/metabolism ; Kelch Repeat ; Phosphoric Diester Hydrolases ; Protozoan Proteins/chemistry ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; Signal Transduction/physiology
Chemical Substances	Cell Cycle Proteins ; Protozoan Proteins ; dct protein, Dictyostelium discoideum ; 8-Bromo Cyclic Adenosine Monophosphate (23583-48-4) ; 8-chloro-cyclic adenosine monophosphate (BQ94Z7E5OR) ; Cyclic AMP (E0399OZS9N) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; Phosphoric Diester Hydrolases (EC 3.1.4.-)
Language	English
Publishing date	2018-04-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020213-1
ISSN	1462-2920 ; 1462-2912
ISSN (online)	1462-2920
ISSN	1462-2912
DOI	10.1111/1462-2920.14126
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Article ; Online: Adaptation in a eukaryotic pathway: combining experiments with modeling.

Rappel, Wouter-Jan / Firtel, Richard A

Cell cycle (Georgetown, Tex.)

2012 Volume 11, Issue 6, Page(s) 1051–1052

Language	English
Publishing date	2012-03-15
Publishing country	United States
Document type	Comment ; Editorial ; Research Support, N.I.H., Extramural
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.4161/cc.11.6.19715
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Article ; Online: The Dictyostelium GSK3 kinase GlkA coordinates signal relay and chemotaxis in response to growth conditions.

Lacal Romero, Jesus / Shen, Zhouxin / Baumgardner, Kimberly / Wei, Jing / Briggs, Steven P / Firtel, Richard A

Developmental biology

2018 Volume 435, Issue 1, Page(s) 56–72

Abstract: GSK3 plays a central role in orchestrating key biological signaling pathways, including cell migration. Here, we identify GlkA as a GSK3 family kinase with functions that overlap with and are distinct from those of GskA. We show that GlkA, as previously ... ...

Abstract	GSK3 plays a central role in orchestrating key biological signaling pathways, including cell migration. Here, we identify GlkA as a GSK3 family kinase with functions that overlap with and are distinct from those of GskA. We show that GlkA, as previously shown for GskA, regulates the cell's cytoskeleton through MyoII assembly and control of Ras and Rap1 function, leading to aberrant cell migration. However, there are both qualitative and quantitative differences in the regulation of Ras and Rap1 and their downstream effectors, including PKB, PKBR1, and PI3K, with glkA
MeSH term(s)	Chemotaxis/physiology ; Dictyostelium/enzymology ; Dictyostelium/genetics ; Gene Expression Regulation, Enzymologic/physiology ; Glycogen Synthase Kinase 3/biosynthesis ; Glycogen Synthase Kinase 3/genetics ; Protozoan Proteins/biosynthesis ; Protozoan Proteins/genetics ; Signal Transduction/physiology
Chemical Substances	Protozoan Proteins ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
Language	English
Publishing date	2018--01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2018.01.007
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Article ; Online: Connecting G protein signaling to chemoattractant-mediated cell polarity and cytoskeletal reorganization.

Liu, Youtao / Lacal, Jesus / Firtel, Richard A / Kortholt, Arjan

Small GTPases

2016 Volume 9, Issue 4, Page(s) 360–364

Abstract: The directional movement toward extracellular chemical gradients, a process called chemotaxis, is an important property of cells. Central to eukaryotic chemotaxis is the molecular mechanism by which chemoattractant-mediated activation of G-protein ... ...

Abstract	The directional movement toward extracellular chemical gradients, a process called chemotaxis, is an important property of cells. Central to eukaryotic chemotaxis is the molecular mechanism by which chemoattractant-mediated activation of G-protein coupled receptors (GPCRs) induces symmetry breaking in the activated downstream signaling pathways. Studies with mainly Dictyostelium and mammalian neutrophils as experimental systems have shown that chemotaxis is mediated by a complex network of signaling pathways. Recently, several labs have used extensive and efficient proteomic approaches to further unravel this dynamic signaling network. Together these studies showed the critical role of the interplay between heterotrimeric G-protein subunits and monomeric G proteins in regulating cytoskeletal rearrangements during chemotaxis. Here we highlight how these proteomic studies have provided greater insight into the mechanisms by which the heterotrimeric G protein cycle is regulated, how heterotrimeric G proteins-induced symmetry breaking is mediated through small G protein signaling, and how symmetry breaking in G protein signaling subsequently induces cytoskeleton rearrangements and cell migration.
MeSH term(s)	Animals ; Cell Polarity ; Chemotaxis ; Cytoskeleton/metabolism ; GTP-Binding Proteins/metabolism ; Humans
Chemical Substances	GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2016-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2682247-7
ISSN	2154-1256 ; 2154-1248
ISSN (online)	2154-1256
ISSN	2154-1248
DOI	10.1080/21541248.2016.1235390
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Article ; Online: "TORCing" neutrophil chemotaxis.

Charest, Pascale G / Firtel, Richard A

Developmental cell

2010 Volume 19, Issue 6, Page(s) 795–796

Abstract: During cell migration, chemoattractant-induced signaling pathways determine the direction of movement by controlling the spatiotemporal dynamics of cytoskeletal components. In this issue of Developmental Cell, Liu et al. report that the target of ... ...

Abstract	During cell migration, chemoattractant-induced signaling pathways determine the direction of movement by controlling the spatiotemporal dynamics of cytoskeletal components. In this issue of Developmental Cell, Liu et al. report that the target of rapamycin complex 2 (TORC2) controls cell polarity and chemotaxis through regulation of both F-actin and myosin II in migrating neutrophils.
Language	English
Publishing date	2010-12-08
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2010.11.017
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Article ; Online: Spatiotemporal regulation of Ras-GTPases during chemotaxis.

Sasaki, Atsuo T / Firtel, Richard A

Methods in molecular biology (Clifton, N.J.)

2009 Volume 571, Page(s) 333–348

Abstract: Many eukaryotic cells can elicit intracellular signaling relays to produce pseudopodia and move up to the chemoattractant gradient (chemotaxis) or move randomly in the absence of extracellular stimuli and nutrients (random movement). A precise ... ...

Abstract	Many eukaryotic cells can elicit intracellular signaling relays to produce pseudopodia and move up to the chemoattractant gradient (chemotaxis) or move randomly in the absence of extracellular stimuli and nutrients (random movement). A precise spatiotemporal regulation of Ras-GTPases, such as Ras and Rap, is crucial to induce pseudopodia formation and cellular adhesion during the chemotaxis and random movement. Here, we describe biochemical and real-time imaging methods for using Dictyostelium to understand the signaling events important for chemotaxis and random cell movement. The chapter includes (1) a biochemical method to assess Ras and Rap1 activation in response to chemoattractant, (2) an imaging method to detect endogenous Ras and Rap1 activation in moving cells, and (3) a simultaneous imaging method to decipher the precise order and localization of these signaling events. With a combination of powerful Dictyostelium genetics, these methods will facilitate to elucidate a dynamic activation of Ras proteins and their inter relay with other signaling molecules during chemotaxis and random movement.
MeSH term(s)	Animals ; Chemotactic Factors/pharmacology ; Chemotaxis/physiology ; Dictyostelium/drug effects ; Dictyostelium/enzymology ; Dictyostelium/metabolism ; GTP Phosphohydrolases/genetics ; GTP Phosphohydrolases/metabolism ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; rap1 GTP-Binding Proteins/genetics ; rap1 GTP-Binding Proteins/metabolism ; ras Proteins/genetics ; ras Proteins/metabolism
Chemical Substances	Chemotactic Factors ; Protozoan Proteins ; GTP Phosphohydrolases (EC 3.6.1.-) ; rap1 GTP-Binding Proteins (EC 3.6.5.2) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2009
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-60761-198-1_23
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Article: Directional sensing during chemotaxis.

Janetopoulos, Christopher / Firtel, Richard A

FEBS letters

2008 Volume 582, Issue 14, Page(s) 2075–2085

Abstract: Cells have the innate ability to sense and move towards a variety of chemoattractants. We investigate the pathways by which cells sense and respond to chemoattractant gradients. We focus on the model system Dictyostelium and compare our understanding of ... ...

Abstract	Cells have the innate ability to sense and move towards a variety of chemoattractants. We investigate the pathways by which cells sense and respond to chemoattractant gradients. We focus on the model system Dictyostelium and compare our understanding of chemotaxis in this system with recent advances made using neutrophils and other mammalian cell types, which share many molecular components and signaling pathways with Dictyostelium. This review also examines models that have been proposed to explain how cells are able to respond to small differences in ligand concentrations between the anterior leading edge and posterior of the cell. In addition, we highlight the overlapping functions of many signaling components in diverse processes beyond chemotaxis, including random cell motility and cell division.
MeSH term(s)	Animals ; Cell Division ; Chemotactic Factors/metabolism ; Chemotaxis ; Dictyostelium/metabolism ; Dictyostelium/physiology ; Feedback, Physiological ; Humans ; Mice ; Microtubules/physiology ; Models, Animal ; Phosphatidylinositols/metabolism ; Signal Transduction
Chemical Substances	Chemotactic Factors ; Phosphatidylinositols ; phosphoinositide-3,4,5-triphosphate
Language	English
Publishing date	2008-04-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1016/j.febslet.2008.04.035
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Article ; Online: Cooperative cell motility during tandem locomotion of amoeboid cells.

Bastounis, Effie / Álvarez-González, Begoña / del Álamo, Juan C / Lasheras, Juan C / Firtel, Richard A

Molecular biology of the cell

2016 Volume 27, Issue 8, Page(s) 1262–1271

Abstract: Streams of migratory cells are initiated by the formation of tandem pairs of cells connected head to tail to which other cells subsequently adhere. The mechanisms regulating the transition from single to streaming cell migration remain elusive, although ... ...

Abstract	Streams of migratory cells are initiated by the formation of tandem pairs of cells connected head to tail to which other cells subsequently adhere. The mechanisms regulating the transition from single to streaming cell migration remain elusive, although several molecules have been suggested to be involved. In this work, we investigate the mechanics of the locomotion ofDictyosteliumtandem pairs by analyzing the spatiotemporal evolution of their traction adhesions (TAs). We find that in migrating wild-type tandem pairs, each cell exerts traction forces on stationary sites (∼80% of the time), and the trailing cell reuses the location of the TAs of the leading cell. Both leading and trailing cells form contractile dipoles and synchronize the formation of new frontal TAs with ∼54-s time delay. Cells not expressing the lectin discoidin I or moving on discoidin I-coated substrata form fewer tandems, but the trailing cell still reuses the locations of the TAs of the leading cell, suggesting that discoidin I is not responsible for a possible chemically driven synchronization process. The migration dynamics of the tandems indicate that their TAs' reuse results from the mechanical synchronization of the leading and trailing cells' protrusions and retractions (motility cycles) aided by the cell-cell adhesions.
MeSH term(s)	Biomechanical Phenomena ; Cell Adhesion ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Cell Movement/physiology ; Dictyostelium/cytology ; Dictyostelium/genetics ; Discoidins/genetics ; Discoidins/metabolism
Chemical Substances	Cell Adhesion Molecules ; Discoidins
Language	English
Publishing date	2016-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E15-12-0836
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Article ; Online: Big roles for small GTPases in the control of directed cell movement.

Charest, Pascale G / Firtel, Richard A

The Biochemical journal

2007 Volume 401, Issue 2, Page(s) 377–390

Abstract: Small GTPases are involved in the control of diverse cellular behaviours, including cellular growth, differentiation and motility. In addition, recent studies have revealed new roles for small GTPases in the regulation of eukaryotic chemotaxis. Efficient ...

Abstract	Small GTPases are involved in the control of diverse cellular behaviours, including cellular growth, differentiation and motility. In addition, recent studies have revealed new roles for small GTPases in the regulation of eukaryotic chemotaxis. Efficient chemotaxis results from co-ordinated chemoattractant gradient sensing, cell polarization and cellular motility, and accumulating data suggest that small GTPase signalling plays a central role in each of these processes as well as in signal relay. The present review summarizes these recent findings, which shed light on the molecular mechanisms by which small GTPases control directed cell migration.
MeSH term(s)	Actins/metabolism ; Animals ; Cell Movement/physiology ; Cell Polarity/physiology ; Chemotaxis/physiology ; GTP Phosphohydrolases/physiology ; GTP-Binding Proteins/physiology ; Guanine Nucleotide Exchange Factors/physiology ; Microtubules/drug effects ; Microtubules/physiology ; Myosins/metabolism ; PTEN Phosphohydrolase/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction/physiology ; ras Proteins/physiology
Chemical Substances	Actins ; Guanine Nucleotide Exchange Factors ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; GTP Phosphohydrolases (EC 3.6.1.-) ; GTP-Binding Proteins (EC 3.6.1.-) ; Myosins (EC 3.6.4.1) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2007-01-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BJ20061432
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