scholarly journals The Fertilization Enigma: How Sperm and Egg Fuse

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Victoria E. Deneke ◽  
Andrea Pauli
Keyword(s):  
Viral Entry ◽  
Molecular Mechanisms ◽  
Muscle Development ◽  
Annual Review ◽  
Publication Date ◽  
Open Questions ◽  
Singular Event ◽  
Multistep Process ◽  
Mammalian Fertilization ◽  
Emerging Themes

Fertilization is a multistep process that culminates in the fusion of sperm and egg, thus marking the beginning of a new organism in sexually reproducing species. Despite its importance for reproduction, the molecular mechanisms that regulate this singular event, particularly sperm–egg fusion, have remained mysterious for many decades. Here, we summarize our current molecular understanding of sperm–egg interaction, focusing mainly on mammalian fertilization. Given the fundamental importance of sperm–egg fusion yet the lack of knowledge of this process in vertebrates, we discuss hallmarks and emerging themes of cell fusion by drawing from well-studied examples such as viral entry, placenta formation, and muscle development. We conclude by identifying open questions and exciting avenues for future studies in gamete fusion. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Molecular Force Measurement with Tension Sensors

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Lisa S. Fischer ◽  
Srishti Rangarajan ◽  
Tanmay Sadhanasatish ◽  
Carsten Grashoff
Keyword(s):  
Molecular Mechanisms ◽  
Force Measurement ◽  
Annual Review ◽  
Publication Date ◽  
Mechanical Forces ◽  
Biophysical Parameters ◽  
Cellular Mechanotransduction ◽  
Molecular Force ◽  
Molecular Forces ◽  
Physical Principles

The ability of cells to generate mechanical forces, but also to sense, adapt to, and respond to mechanical signals, is crucial for many developmental, postnatal homeostatic, and pathophysiological processes. However, the molecular mechanisms underlying cellular mechanotransduction have remained elusive for many decades, as techniques to visualize and quantify molecular forces across individual proteins in cells were missing. The development of genetically encoded molecular tension sensors now allows the quantification of piconewton-scale forces that act upon distinct molecules in living cells and even whole organisms. In this review, we discuss the physical principles, advantages, and limitations of this increasingly popular method. By highlighting current examples from the literature, we demonstrate how molecular tension sensors can be utilized to obtain access to previously unappreciated biophysical parameters that define the propagation of mechanical forces on molecular scales. We discuss how the methodology can be further developed and provide a perspective on how the technique could be applied to uncover entirely novel aspects of mechanobiology in the future. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Ecology and Evolution of Model Microbial Mutualisms

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Jeremy M. Chacón ◽  
Sarah P. Hammarlund ◽  
Jonathan N.V. Martinson ◽  
Leno B. Smith ◽  
William R. Harcombe
Keyword(s):  
Future Study ◽  
Evolutionary Dynamics ◽  
Interspecific Interactions ◽  
Natural World ◽  
Annual Review ◽  
Publication Date ◽  
Controlled Experiments ◽  
Evolutionary Origins ◽  
Ecological Features ◽  
Open Questions

Mutually beneficial interspecific interactions are abundant throughout the natural world, including between microbes. Mutualisms between microbes are critical for everything from human health to global nutrient cycling. Studying model microbial mutualisms in the laboratory enables highly controlled experiments for developing and testing evolutionary and ecological hypotheses. In this review, we begin by describing the tools available for studying model microbial mutualisms. We then outline recent insights that laboratory systems have shed on the evolutionary origins, evolutionary dynamics, and ecological features of microbial mutualism. We touch on gaps in our current understanding of microbial mutualisms, note connections to mutualism in nonmicrobial systems, and call attention to open questions ripe for future study. Expected final online publication date for the Annual Review of Ecology, Evolution, and Systematics, Volume 52 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Regulatory Themes and Variations by the Stress-Signaling Nucleotide Alarmones (p)ppGpp in Bacteria

2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Brent W. Anderson ◽  
Danny K. Fung ◽  
Jue D. Wang
Keyword(s):  
Metabolic Regulation ◽  
Protein Translation ◽  
Annual Review ◽  
Publication Date ◽  
Stress Signaling ◽  
Nucleotide Synthesis ◽  
Evolutionary Diversification ◽  
Metabolic Remodeling ◽  
Emerging Themes ◽  
Metabolic Interconversion

Bacterial stress-signaling alarmones are important components of a protective network against diverse stresses such as nutrient starvation and antibiotic assault. pppGpp and ppGpp, collectively (p)ppGpp, have well-documented regulatory roles in gene expression and protein translation. Recent work has highlighted another key function of (p)ppGpp: inducing rapid and coordinated changes in cellular metabolism by regulating enzymatic activities, especially those involved in purine nucleotide synthesis. Failure of metabolic regulation by (p)ppGpp results in the loss of coordination between metabolic and macromolecular processes, leading to cellular toxicity. In this review, we document how (p)ppGpp and newly characterized nucleotides pGpp and (p)ppApp directly regulate these enzymatic targets for metabolic remodeling. We examine targets’ common determinants for alarmone interaction as well as their evolutionary diversification. We highlight classical and emerging themes in nucleotide signaling, including oligomerization and allostery along with metabolic interconversion and crosstalk, illustrating how they allow optimized bacterial adaptation to their environmental niches. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Systems Biology of the Vasopressin V2 Receptor: New Tools for Discovery of Molecular Actions of a GPCR

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Lihe Chen ◽  
Hyun Jun Jung ◽  
Arnab Datta ◽  
Euijung Park ◽  
Brian G. Poll ◽  
...  
Keyword(s):  
Systems Biology ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Water Channel ◽  
Peptide Hormone ◽  
Annual Review ◽  
Publication Date ◽  
Large Scale Data ◽  
V2 Receptor ◽  
Scale Data

Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing–based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailed framework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Molecules from the Microbiome

2021 ◽  
Vol 90 (1) ◽  
Author(s):  
Emilee E. Shine ◽  
Jason M. Crawford
Keyword(s):  
Small Molecules ◽  
Molecular Mechanisms ◽  
System Development ◽  
Human Microbiome ◽  
Host Responses ◽  
Annual Review ◽  
Publication Date ◽  
Mechanistic Studies ◽  
Immune System Development ◽  
Interdisciplinary Approaches

The human microbiome encodes a second genome that dwarfs the genetic capacity of the host. Microbiota-derived small molecules can directly target human cells and their receptors or indirectly modulate host responses through functional interactions with other microbes in their ecological niche. Their biochemical complexity has profound implications for nutrition, immune system development, disease progression, and drug metabolism, as well as the variation in these processes that exists between individuals. While the species composition of the human microbiome has been deeply explored, detailed mechanistic studies linking specific microbial molecules to host phenotypes are still nascent. In this review, we discuss challenges in decoding these interaction networks, which require interdisciplinary approaches that combine chemical biology, microbiology, immunology, genetics, analytical chemistry, bioinformatics, and synthetic biology. We highlight important classes of microbiota-derived small molecules and notable examples. An understanding of these molecular mechanisms is central to realizing the potential of precision microbiome editing in health, disease, and therapeutic responses. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Microbiota Effects on Carcinogenesis: Initiation, Promotion and Progression

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Lacey R. Lopez ◽  
Rachel M. Bleich ◽  
Janelle C. Arthur
Keyword(s):  
Immune Evasion ◽  
Fusobacterium Nucleatum ◽  
Cancer Development ◽  
Annual Review ◽  
Publication Date ◽  
Epigenetic Changes ◽  
Microbial Activities ◽  
Normal Cells ◽  
Multistep Process ◽  
Host Genetic

Carcinogenesis is a multistep process by which normal cells acquire genetic and epigenetic changes that result in cancer. In combination with host genetic susceptibility and environmental exposures, a prominent procarcinogenic role for the microbiota has recently emerged. In colorectal cancer (CRC), three nefarious microbes have been consistently linked to cancer development: ( a) Colibactin-producing Escherichia coli initiates carcinogenic DNA damage, ( b) enterotoxigenic Bacteroides fragilis promotes tumorigenesis via toxin-induced cell proliferation and tumor-promoting inflammation, and ( c) Fusobacterium nucleatum enhances CRC progression through two adhesins, Fap2 and FadA, that promote proliferation and antitumor immune evasion and may contribute to metastases. Herein, we use these three prominent microbes to discuss the experimental evidence linking microbial activities to carcinogenesis and the specific mechanisms driving this stepwise process. Precisely defining mechanisms by which the microbiota impacts carcinogenesis at each stage is essential for developing microbiota-targeted strategies for the diagnosis, prognosis, and treatment of cancer. Expected final online publication date for the Annual Review of Medicine, Volume 72 is January 27, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Mitochondrial H+ Leak and Thermogenesis

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Ambre M. Bertholet ◽  
Yuriy Kirichok
Keyword(s):  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Annual Review ◽  
Publication Date ◽  
Uncoupling Protein 1 ◽  
Current Field ◽  
Atp Production ◽  
Metabolic Substrates ◽  
Primary Focus

Mitochondria of all tissues convert various metabolic substrates into two forms of energy: ATP and heat. Historically, the primary focus of research in mitochondrial bioenergetics was on the mechanisms of ATP production, while mitochondrial thermogenesis received significantly less attention. Nevertheless, mitochondrial heat production is crucial for the maintenance of body temperature, regulation of the pace of metabolism, and prevention of oxidative damage to mitochondria and the cell. In addition, mitochondrial thermogenesis has gained significance as a pharmacological target for treating metabolic disorders. Mitochondria produce heat as the result of H+ leak across their inner membrane. This review provides a critical assessment of the current field of mitochondrial H+ leak and thermogenesis, with a focus on the molecular mechanisms involved in the function and regulation of uncoupling protein 1 and the ADP/ATP carrier, the two proteins that mediate mitochondrial H+ leak. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Adipose Tissue Fibrosis in Obesity: Etiology and Challenges

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Geneviève Marcelin ◽  
Emmanuel L. Gautier ◽  
Karine Clément
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Annual Review ◽  
Publication Date ◽  
Tissue Fibrosis ◽  
Adipose Tissue Remodeling ◽  
Metabolic Dysfunctions ◽  
Body Energy

Obesity is a chronic and progressive process affecting whole-body energy balance and is associated with comorbidities development. In addition to increased fat mass, obesity induces white adipose tissue (WAT) inflammation and fibrosis, leading to local and systemic metabolic dysfunctions, such as insulin resistance (IR). Accordingly, limiting inflammation or fibrosis deposition may improve IR and glucose homeostasis. Although no targeted therapy yet exists to slow or reverse adipose tissue fibrosis, a number of findings have clarified the underlying cellular and molecular mechanisms. In this review, we highlight adipose tissue remodeling events shown to be associated with fibrosis deposition, with a focus on adipose progenitors involved in obesity-induced healthy as well as unhealthy WAT expansion. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Receptor-Ribosome Coupling: A Link Between Extrinsic Signals and mRNA Translation in Neuronal Compartments

2022 ◽  
Vol 45 (1) ◽  
Author(s):  
Max Koppers ◽  
Christine E. Holt
Keyword(s):  
Intracellular Signaling ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Cell Communication ◽  
Mrna Translation ◽  
Common Mechanism ◽  
Annual Review ◽  
Publication Date ◽  
Spatiotemporal Resolution

Axons receive extracellular signals that help to guide growth and synapse formation during development and to maintain neuronal function and survival during maturity. These signals relay information via cell surface receptors that can initiate local intracellular signaling at the site of binding, including local messenger RNA (mRNA) translation. Direct coupling of translational machinery to receptors provides an attractive way to activate this local mRNA translation and change the local proteome with high spatiotemporal resolution. Here, we first discuss the increasing evidence that different external stimuli trigger translation of specific subsets of mRNAs in axons via receptors and thus play a prominent role in various processes in both developing and mature neurons. We then discuss the receptor-mediated molecular mechanisms that regulate local mRNA translational with a focus on direct receptor-ribosome coupling. We advance the idea that receptor-ribosome coupling provides several advantages over other translational regulation mechanisms and is a common mechanism in cell communication. Expected final online publication date for the Annual Review of Neuroscience, Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Enteroviruses and Type 1 Diabetes: Multiple Mechanisms and Factors?

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Richard E. Lloyd ◽  
Manasi Tamhankar ◽  
Åke Lernmark
Keyword(s):  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Subsequent Development ◽  
Annual Review ◽  
Publication Date ◽  
Virus Infections ◽  
Persistent Infections ◽  
Complex Interactions ◽  
Genetic And Environmental Factors

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency and resultant hyperglycemia. Complex interactions of genetic and environmental factors trigger the onset of autoimmune mechanisms responsible for development of autoimmunity to β cell antigens and subsequent development of T1D. A potential role of virus infections has long been hypothesized, and growing evidence continues to implicate enteroviruses as the most probable triggering viruses. Recent studies have strengthened the association between enteroviruses and development of autoimmunity in T1D patients, potentially through persistent infections. Enterovirus infections may contribute to different stages of disease development. We review data from both human cohort studies and experimental research exploring the potential roles and molecular mechanisms by which enterovirus infections can impact disease outcome. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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