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Article: Bacterial Autophagy: Offense and Defense at the Host-Pathogen Interface.

Casanova, James E

Cellular and molecular gastroenterology and hepatology

2017 Volume 4, Issue 2, Page(s) 237–243

Abstract: Autophagy is a fundamental cellular process used for the turnover and recycling of cytosolic components and damaged organelles. Originally characterized as a response to cellular stress, it now is well established that autophagy also is used as a ... ...

Abstract	Autophagy is a fundamental cellular process used for the turnover and recycling of cytosolic components and damaged organelles. Originally characterized as a response to cellular stress, it now is well established that autophagy also is used as a defensive mechanism to combat the infection of host cells by intracellular pathogens. However, although this defensive strategy does limit the proliferation of most pathogens within their host cells, successful pathogens have evolved countermeasures that subvert or circumvent the autophagic response. In this review, we discuss the mechanisms used by a number of these pathogens to escape autophagy, with a particular focus on
Language	English
Publishing date	2017-09
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2352-345X
ISSN	2352-345X
DOI	10.1016/j.jcmgh.2017.05.002
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Article ; Online: Quantitation of RhoA activation: differential binding to downstream effectors.

Zhang, Yu-Wen / Torsilieri, Holly M / Casanova, James E

Small GTPases

2022 Volume 13, Issue 1, Page(s) 296–306

Abstract: The small GTPase RhoA controls many important cellular processes through its ability to activate multiple downstream effector pathways. Most RhoA effectors contain a Rho-binding domain (RBD), and interaction between active RhoA and the RBD typically ... ...

Abstract	The small GTPase RhoA controls many important cellular processes through its ability to activate multiple downstream effector pathways. Most RhoA effectors contain a Rho-binding domain (RBD), and interaction between active RhoA and the RBD typically induces a conformational change in effectors that stimulates their recruitment or activity. Isolated GTPase binding domains fused to GST have been widely used in so-called pulldown assays to measure the activation state of other GTPases in cell lysates. Similarly, GST fusions containing the RBD of the RhoA effector Rhotekin have been widely adopted as a standardized tool for the measurement of RhoA activation. RBDs have also been used to generate fluorescent reporter constructs to localize sites of GTPase activation in intact cells. In this report, we demonstrate that not all forms of active RhoA are capable of interacting with the Rhotekin RBD. A constitutively active RhoA-G14V mutant, which interacted with the RBDs of ROCK2 and mDIA1, was unable to bind the Rhotekin RBD as evidenced by both conventional GST pulldown assay and our newly established BRET assay. Furthermore, active RhoA induced by different stimuli in cells also displayed binding preference for its diverse effectors. Our data demonstrate that RhoA may undergo effector-specific activation for differential regulation of its downstream pathways, and that RhoA activation should not be defined solely by its interaction with Rhotekin.
MeSH term(s)	Protein Binding ; rhoA GTP-Binding Protein/metabolism
Chemical Substances	rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2022-11-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2682247-7
ISSN	2154-1256 ; 2154-1248
ISSN (online)	2154-1256
ISSN	2154-1248
DOI	10.1080/21541248.2022.2111945
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Article ; Online: Fat-Free Mass and Total Daily Energy Expenditure Estimated Using Doubly Labeled Water Predict Energy Intake in a Large Sample of Community-Dwelling Older Adults.

Hopkins, Mark / Casanova, Nuno / Finlayson, Graham / Stubbs, R James / Blundell, John E

The Journal of nutrition

2023 Volume 152, Issue 4, Page(s) 971–980

Abstract: Background: Up to 30% of community-based older adults report reduced appetite and energy intake (EI), but previous research examining the underlying physiological mechanisms has focused on the mechanisms that suppress eating rather than the hunger drive ...

Abstract	Background: Up to 30% of community-based older adults report reduced appetite and energy intake (EI), but previous research examining the underlying physiological mechanisms has focused on the mechanisms that suppress eating rather than the hunger drive and EI. Objectives: We examined the associations between fat-free mass (FFM), physical activity (PA), total daily energy expenditure (TDEE), and self-reported EI in older adults. Methods: The present study was a secondary analysis of the Interactive Diet and Activity Tracking in AARP study. Body composition (deuterium dilution), PA (accelerometry), and TDEE (doubly labeled water) were measured in 590 older adults (age, 63.1 ± 5.9 years; BMI, 28.1 ± 4.9 kg/m Results: After controlling for age and sex, linear regression demonstrated that FFM and TDEE predicted EI when estimated from a single 24-hour dietary recall (P < 0.05), from the mean of up to 6 dietary recalls (P < 0.05), and after the removal of those classified as underreporters (P < 0.001). Age moderated the associations between FFM and EI Conclusions: These data suggest that the total daily EI is proportional to the FFM and TDEE, but not fat mass, in older adults. These associations may reflect an underling drive to eat that influences the daily food intake. While the associations between FFM or TDEE and EI existed across all age quintiles, these associations weakened with increasing age.
MeSH term(s)	Humans ; Aged ; Middle Aged ; Water ; Independent Living ; Energy Metabolism/physiology ; Energy Intake/physiology ; Diet ; Body Composition/physiology
Chemical Substances	Water (059QF0KO0R)
Language	English
Publishing date	2023-02-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1093/jn/nxab434
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Article ; Online: Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ-mediated suppression of the host cholesterol transport protein ABCA1.

Greene, Adam R / Owen, Katherine A / Casanova, James E

Cellular microbiology

2021 Volume 23, Issue 8, Page(s) e13329

Abstract: Upon infection of host cells, Salmonella enterica serovar Typhimurium resides in a modified-endosomal compartment referred to as the Salmonella-containing vacuole (SCV). SCV biogenesis is driven by multiple effector proteins translocated through two type ...

Abstract	Upon infection of host cells, Salmonella enterica serovar Typhimurium resides in a modified-endosomal compartment referred to as the Salmonella-containing vacuole (SCV). SCV biogenesis is driven by multiple effector proteins translocated through two type III secretion systems (T3SS-1 and T3SS-2). While many host proteins targeted by these effector proteins have been characterised, the role of host lipids in SCV dynamics remains poorly understood. Previous studies have shown that S. Typhimurium infection in macrophages leads to accumulation of intracellular cholesterol, some of which concentrates in and around SCVs; however, the underlying mechanisms remain unknown. Here, we show that S. Typhimurium utilises the T3SS-2 effector SseJ to downregulate expression of the host cholesterol transporter ABCA1 in macrophages, leading to a ~45% increase in cellular cholesterol. Mechanistically, SseJ activates a signalling cascade involving the host kinases FAK and Akt to suppress Abca1 expression. Mutational inactivation of SseJ acyltransferase activity, silencing FAK, or inhibiting Akt prevents Abca1 downregulation and the corresponding accumulation of cholesterol during infection. Importantly, RNAi-mediated silencing of ABCA1 rescued bacterial survival in FAK-deficient macrophages, suggesting that Abca1 downregulation and cholesterol accumulation are important for intracellular survival.
MeSH term(s)	Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Carrier Proteins ; Cholesterol ; Homeostasis ; Macrophages/metabolism ; Salmonella typhimurium/metabolism
Chemical Substances	Bacterial Proteins ; Carrier Proteins ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2021-04-22
Publishing country	India
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1468320-9
ISSN	1462-5822 ; 1462-5814
ISSN (online)	1462-5822
ISSN	1462-5814
DOI	10.1111/cmi.13329
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Article: Synchrony 2022: Epilepsy and Seizures in Autism Spectrum Disorder Roundtable.

Frye, Richard E / Nanda, Heer / Pleasure, Samuel J / Casanova, Manuel F / Boles, Richard G / Lewine, Jeffrey / Gaitanis, John / Adams, James B

Journal of personalized medicine

2023 Volume 13, Issue 3

Abstract: The BRAIN Foundation (Pleasanton, CA, USA) hosted Synchrony 2022, a translational medicine conference focused on research into treatments for individuals with neurodevelopmental disorders (NDD), including those with autism spectrum disorders (ASD) [ ... ]. ...

Abstract	The BRAIN Foundation (Pleasanton, CA, USA) hosted Synchrony 2022, a translational medicine conference focused on research into treatments for individuals with neurodevelopmental disorders (NDD), including those with autism spectrum disorders (ASD) [...].
Language	English
Publishing date	2023-03-20
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm13030557
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Article ; Online: The mating pilus of

Beltrán, Leticia / Torsilieri, Holly / Patkowski, Jonasz B / Yang, Jie E / Casanova, James / Costa, Tiago R D / Wright, Elizabeth R / Egelman, Edward H

mBio

2023 Volume 15, Issue 1, Page(s) e0285723

Abstract: Importance: Bacteria are constantly exchanging DNA, which constitutes horizontal gene transfer. While some of these occurs by a non-specific process called natural transformation, some occurs by a specific mating between a donor and a recipient cell. In ...

Abstract	Importance: Bacteria are constantly exchanging DNA, which constitutes horizontal gene transfer. While some of these occurs by a non-specific process called natural transformation, some occurs by a specific mating between a donor and a recipient cell. In specific conjugation, the mating pilus is extended from the donor cell to make contact with the recipient cell, but whether DNA is actually transferred through this pilus or by another mechanism involving the type IV secretion system complex without the pilus has been an open question. Using
MeSH term(s)	Escherichia coli/genetics ; Escherichia coli/metabolism ; DNA, Bacterial/genetics ; DNA, Bacterial/metabolism ; Gene Transfer, Horizontal ; Conjugation, Genetic ; Fimbriae, Bacterial/genetics ; Fimbriae, Bacterial/metabolism ; Plasmids
Chemical Substances	DNA, Bacterial
Language	English
Publishing date	2023-12-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.02857-23
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Article ; Online: A new Rab7 effector controls phosphoinositide conversion in endosome maturation.

Casanova, James E / Winckler, Bettina

The Journal of cell biology

2017 Volume 216, Issue 10, Page(s) 2995–2997

Abstract: Endosome maturation requires a coordinated change in the Rab GTPase and phosphoinositide composition of the endosomal membrane. In this issue, Liu et al. (2017. ...

Abstract	Endosome maturation requires a coordinated change in the Rab GTPase and phosphoinositide composition of the endosomal membrane. In this issue, Liu et al. (2017.
MeSH term(s)	Endosomes ; Phosphatidylinositol 3-Kinases ; Phosphatidylinositols ; rab GTP-Binding Proteins
Chemical Substances	Phosphatidylinositols ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; rab GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2017-09-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.201709034
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Article: Advantages and limitations of cell-based assays for GTPase activation and regulation.

Casanova, James E

Cellular logistics

2012 Volume 2, Issue 3, Page(s) 147–150

Abstract: Small GTPases of the Ras superfamily are important regulators of many cellular functions, including signal transduction, cytoskeleton assembly, metabolic regulation, organelle biogenesis and intracellular transport. Most GTPases act as binary switches, ... ...

Abstract	Small GTPases of the Ras superfamily are important regulators of many cellular functions, including signal transduction, cytoskeleton assembly, metabolic regulation, organelle biogenesis and intracellular transport. Most GTPases act as binary switches, being "on" in the active, GTP-bound state and "off" in the inactive, GDP-bound state, and cycle between the two states with the aid of accessory proteins, referred to as guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). This review will focus on the ADP-ribosylation factors (Arfs), a family of G-proteins that are essential regulators of carrier vesicle formation during vesicular transport. As for most other GTPases, the Arfs themselves are vastly outnumbered by the proteins that regulate them, and a major focus in the field has been to define the functional relationships between individual GEFs and GAPs and their substrates at the cellular level. Over the years, a variety of methods have been developed to measure GTPase activation in vitro and in vivo. In vitro analysis will be discussed in the accompanying article by Randazzo and colleagues. Here we will focus on cell- and tissue-based assays and their advantages/disadvantages relative to cell-free systems.
Language	English
Publishing date	2012-06-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2682440-1
ISSN	2159-2799 ; 2159-2780
ISSN (online)	2159-2799
ISSN	2159-2780
DOI	10.4161/cl.22045
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Article ; Online: Fat-Free Mass and Total Daily Energy Expenditure Estimated Using Doubly Labeled Water Predict Energy Intake in a Large Sample of Community-Dwelling Older Adults.

Hopkins, Mark / Casanova, Nuno / Finlayson, Graham / Stubbs, R James / Blundell, John E

The Journal of nutrition

2021 Volume 152, Issue 4, Page(s) 971–980

Abstract	Background: Up to 30% of community-based older adults report reduced appetite and energy intake (EI), but previous research examining the underlying physiological mechanisms has focused on the mechanisms that suppress eating rather than the hunger drive and EI. Objectives: We examined the associations between fat-free mass (FFM), physical activity (PA), total daily energy expenditure (TDEE), and self-reported EI in older adults. Methods: The present study was a secondary analysis of the Interactive Diet and Activity Tracking in AARP study. Body composition (deuterium dilution), PA (accelerometry), and TDEE (doubly labeled water) were measured in 590 older adults (age, 63.1 ± 5.9 years; BMI, 28.1 ± 4.9 kg/m2). The total daily EI was estimated from a single 24-hour dietary recall (EIsingle; ±1 month of PA and TDEE measurement) and the mean of up to 6 recalls over a 12-month period (EImean), with misreporters classified using the 95% CIs between the EImean and TDEE. Results: After controlling for age and sex, linear regression demonstrated that FFM and TDEE predicted EI when estimated from a single 24-hour dietary recall (P < 0.05), from the mean of up to 6 dietary recalls (P < 0.05), and after the removal of those classified as underreporters (P < 0.001). Age moderated the associations between FFM and EIsingle (P < 0.001), FFM and EImean (P < 0.001), and TDEE with EIsingle (P = 0.016), with associations becoming weaker across age quintiles. Conclusions: These data suggest that the total daily EI is proportional to the FFM and TDEE, but not fat mass, in older adults. These associations may reflect an underling drive to eat that influences the daily food intake. While the associations between FFM or TDEE and EI existed across all age quintiles, these associations weakened with increasing age.
MeSH term(s)	Aged ; Body Composition/physiology ; Energy Intake ; Energy Metabolism/physiology ; Humans ; Independent Living ; Middle Aged ; Water
Chemical Substances	Water (059QF0KO0R)
Language	English
Publishing date	2021-12-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1093/jn/nxab434
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Article ; Online: Salmonella Manipulates Autophagy to "Serve and Protect".

Owen, Katherine A / Casanova, James E

Cell host & microbe

2015 Volume 18, Issue 5, Page(s) 517–519

Abstract: Many intracellular pathogens, including Salmonella typhimurium, trigger autophagy in host cells, which is widely thought to restrict intracellular growth and survival. In this issue of Cell Host & Microbe, Kreibich et al. (2015) demonstrate a role for ... ...

Abstract	Many intracellular pathogens, including Salmonella typhimurium, trigger autophagy in host cells, which is widely thought to restrict intracellular growth and survival. In this issue of Cell Host & Microbe, Kreibich et al. (2015) demonstrate a role for the autophagic machinery in the repair of damaged Salmonella-containing vacuoles (SCVs).
MeSH term(s)	Autophagy ; Cytoplasm ; Humans ; Salmonella Infections ; Salmonella typhimurium ; Vacuoles
Language	English
Publishing date	2015-11-16
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2015.10.020
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