Effects of neuronal drebrin on actin dynamics

2021 ◽  
Author(s):  
Elena E. Grintsevich
Keyword(s):  
Synaptic Plasticity ◽  
Posttranslational Modifications ◽  
Neurodegenerative Disorders ◽  
Neuronal Migration ◽  
Recent Progress ◽  
Actin Dynamics ◽  
Cytoskeletal Dynamics ◽  
Health And Disease ◽  
Made In

Drebrin is a key regulator of actin cytoskeleton in neuronal cells which is critical for synaptic plasticity, neuritogenesis, and neuronal migration. It is also known to orchestrate a cross-talk between actin and microtubules. Decreased level of drebrin is a hallmark of multiple neurodegenerative disorders such as Alzheimer's disease. Despite its established importance in health and disease, we still have a lot to learn about drebrin's interactome and its effects on cytoskeletal dynamics. This review aims to summarize the recently reported novel effects of drebrin on actin and its regulators. Here I will also reflect on the most recent progress made in understanding of the role of drebrin isoforms and posttranslational modifications on its functionality.

scholarly journals Presynaptic AMPA Receptors in Health and Disease

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2260
Author(s):  
Letizia Zanetti ◽  
Maria Regoni ◽  
Elena Ratti ◽  
Flavia Valtorta ◽  
Jenny Sassone
Keyword(s):  
Ampa Receptors ◽  
Plasma Membranes ◽  
Actin Dynamics ◽  
Axonal Pathology ◽  
Pathological Conditions ◽  
Pain Transmission ◽  
Pharmacological Targets ◽  
Health And Disease ◽  
Excitatory Neurotransmission

AMPA receptors (AMPARs) are ionotropic glutamate receptors that play a major role in excitatory neurotransmission. AMPARs are located at both presynaptic and postsynaptic plasma membranes. A huge number of studies investigated the role of postsynaptic AMPARs in the normal and abnormal functioning of the mammalian central nervous system (CNS). These studies highlighted that changes in the functional properties or abundance of postsynaptic AMPARs are major mechanisms underlying synaptic plasticity phenomena, providing molecular explanations for the processes of learning and memory. Conversely, the role of AMPARs at presynaptic terminals is as yet poorly clarified. Accruing evidence demonstrates that presynaptic AMPARs can modulate the release of various neurotransmitters. Recent studies also suggest that presynaptic AMPARs may possess double ionotropic-metabotropic features and that they are involved in the local regulation of actin dynamics in both dendritic and axonal compartments. In addition, evidence suggests a key role of presynaptic AMPARs in axonal pathology, in regulation of pain transmission and in the physiology of the auditory system. Thus, it appears that presynaptic AMPARs play an important modulatory role in nerve terminal activity, making them attractive as novel pharmacological targets for a variety of pathological conditions.

Role of autophagy in cancer prevention, development and therapy

2013 ◽  
Vol 55 ◽  
pp. 133-151 ◽  
Author(s):  
G. Vignir Helgason ◽  
Tessa L. Holyoake ◽  
Kevin M. Ryan
Keyword(s):  
Quality Control ◽  
Clinical Trials ◽  
Cancer Prevention ◽  
Mammalian Cells ◽  
Physiological Role ◽  
Anticancer Therapy ◽  
Substantial Progress ◽  
Health And Disease ◽  
Made In

Autophagy is a process that takes place in all mammalian cells and ensures homoeostasis and quality control. The term autophagy [self (auto)-eating (phagy)] was first introduced in 1963 by Christian de Duve, who discovered the involvement of lysosomes in the autophagy process. Since then, substantial progress has been made in understanding the molecular mechanism and signalling regulation of autophagy and several reviews have been published that comprehensively summarize these findings. The role of autophagy in cancer has received a lot of attention in the last few years and autophagy modulators are now being tested in several clinical trials. In the present chapter we aim to give a brief overview of recent findings regarding the mechanism and key regulators of autophagy and discuss the important physiological role of mammalian autophagy in health and disease. Particular focus is given to the role of autophagy in cancer prevention, development and in response to anticancer therapy. In this regard, we also give an updated list and discuss current clinical trials that aim to modulate autophagy, alone or in combination with radio-, chemo- or targeted therapy, for enhanced anticancer intervention.

scholarly journals Use of Lipid-Modifying Agents for the Treatment of Glomerular Diseases

2021 ◽  
Vol 11 (8) ◽  
pp. 820
Author(s):  
Mengyuan Ge ◽  
Sandra Merscher ◽  
Alessia Fornoni
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Recent Progress ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Glomerular Diseases ◽  
Intracellular Lipids ◽  
Lipid Modifying Agents ◽  
Made In

Although dyslipidemia is associated with chronic kidney disease (CKD), it is more common in nephrotic syndrome (NS), and guidelines for the management of hyperlipidemia in NS are largely opinion-based. In addition to the role of circulating lipids, an increasing number of studies suggest that intrarenal lipids contribute to the progression of glomerular diseases, indicating that proteinuric kidney diseases may be a form of “fatty kidney disease” and that reducing intracellular lipids could represent a new therapeutic approach to slow the progression of CKD. In this review, we summarize recent progress made in the utilization of lipid-modifying agents to lower renal parenchymal lipid accumulation and to prevent or reduce kidney injury. The agents mentioned in this review are categorized according to their specific targets, but they may also regulate other lipid-relevant pathways.

scholarly journals Decoding natural astrocyte rhythms: dynamic actin waves result from environmental sensing by primary rodent astrocytes

2021 ◽  
Author(s):  
Kate M. O’Neill ◽  
Emanuela Saracino ◽  
Barbara Barile ◽  
Nicholas J. Mennona ◽  
Maria Grazia Mola ◽  
...  
Keyword(s):  
Water Concentration ◽  
Cell Boundary ◽  
Actin Dynamics ◽  
Substrate Topography ◽  
Actin Cortex ◽  
Extraction Algorithm ◽  
Cytoskeletal Dynamics ◽  
Actin Structure ◽  
Actin Waves

AbstractAstrocytes are key regulators of brain homeostasis, which is essential for proper cognitive function. The role of cytoskeletal dynamics in this critical regulatory process is unknown. Here we find that actin is dynamic in certain subcellular regions, especially near the cell boundary. Our results further indicate that actin dynamics concentrates into “hotspot” regions that selectively respond to certain chemophysical stimuli, specifically the homeostatic challenges of ion or water concentration increases. Substrate topography makes actin dynamics more frequent yet weaker, and it also alters actin network structure. Superresolution images analyzed with a filament extraction algorithm demonstrate that surface topography is associated with a predominant perpendicular alignment of actin filaments near the cell boundary whereas flat substrates result in an actin cortex mainly parallel to the cell boundary. Thus, actin structure and dynamics together integrate information from different aspects of the environment that might steer the operation of neural cell networks.TeaserAstrocytes display dynamic actin that is modulated by combinations of chemophysical stimuli and environmental topographies.

Mast cells in health and disease

2011 ◽  
Vol 120 (11) ◽  
pp. 473-484 ◽  
Author(s):  
Charlotte L. Weller ◽  
Sarah J. Collington ◽  
Tim Williams ◽  
Jonathan R. Lamb
Keyword(s):  
Wound Healing ◽  
Mast Cells ◽  
Allergic Disease ◽  
Effector Functions ◽  
Health And Disease ◽  
Developing Area ◽  
Deficient Mice ◽  
Made In

Although MCs (mast cells) were discovered over 100 years ago, for the majority of this time their function was linked almost exclusively to allergy and allergic disease with few other roles in health and disease. The engineering of MC-deficient mice and engraftment of these mice with MCs deficient in receptors or mediators has advanced our knowledge of the role of MCs in vivo. It is now known that MCs have very broad and varied roles in both physiology and disease which will be reviewed here with a focus on some of the most recent discoveries over the last year. MCs can aid in maintaining a healthy physiology by secreting mediators that promote wound healing and homoeostasis as well as interacting with neurons. Major developments have been made in understanding MC function in defence against pathogens, in recognition of pathogens as well as direct effector functions. Probably the most quickly developing area of understanding is the involvement and contribution MCs make in the progression of a variety of diseases from some of the most common diseases to the more obscure.

The universe of Hsp90

2012 ◽  
Vol 3 (1) ◽  
pp. 79-97 ◽  
Author(s):  
Marta Stankiewicz ◽  
Matthias P. Mayer
Keyword(s):  
Posttranslational Modifications ◽  
Optimal Growth ◽  
Growth Conditions ◽  
Special Role ◽  
Regulatory Circuits ◽  
Health And Disease ◽  
Client Proteins ◽  
Essential Function ◽  
Shock Proteins

AbstractMolecular chaperones are key components in the maintenance of cellular homeostasis and survival, not only during stress but also under optimal growth conditions. Among the ATP-dependent chaperones, heat shock proteins (Hsp90) proteins play a special role. While Hsp90s can interact with unfolded and misfolded proteins, their main (and in eukaryotic cells essential) function appears to involve interactions with a limited number of protein clients at late steps of maturation or in “alter-native” conformations for regulating their stability and activity. Because Hsp90 clients are hubs of diverse signaling networks and participate in nearly every cellular function, Hsp90s interconnect many regulatory circuits and link them to environmental impacts. The availability and activity of Hsp90 may thus influence complex physiological and pathophysiological processes, such as differentiation, development, aging, cancer, neurodegeneration, and infectious diseases. Furthermore, through homeostatic effects on differentiation and development, Hsp90s act as capacitors of phenotypic evolution. In this review, we discuss recent insights in the structure and chaperone cycle of Hsp90s, the mechanisms underlying Hsp90 binding to clients, and potential reasons why client proteins specifically require the assistance of Hsp90s. Moreover, the current views on Hsp90-cochaperone interactions and regulation of Hsp90 proteins via posttranslational modifications are summarized. The second half of this article is devoted to the role of Hsp90 proteins in health and disease, aging, and evolution.

Recent progress in understanding the role of Reelin in radial neuronal migration, with specific emphasis on the dentate gyrus

2006 ◽  
Vol 23 (4) ◽  
pp. 901-909 ◽  
Author(s):  
Eckart Förster ◽  
Yves Jossin ◽  
Shanting Zhao ◽  
Xuejun Chai ◽  
Michael Frotscher ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Neuronal Migration ◽  
Recent Progress

scholarly journals The inter-α-inhibitor family: from structure to regulation

1996 ◽  
Vol 315 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Jean-Philippe SALIER ◽  
Philippe ROUET ◽  
Gilda RAGUENEZ ◽  
Maryvonne DAVEAU
Keyword(s):  
Plasma Proteins ◽  
Recent Progress ◽  
Family Members ◽  
Protein Levels ◽  
The Family ◽  
Health And Disease ◽  
Structure Regulation ◽  
Uniform Nomenclature ◽  
Made In

Inter-α-inhibitor (IαI) and related molecules, collectively referred to as the IαI family, are a group of plasma protease inhibitors. They display attractive features such as precursor polypeptides that give rise to mature chains with quite distinct fates and functions, and inter-chain glycosaminoglycan bonds within the various molecules. The discovery of an ever growing number of such molecules has raised pertinent questions about their pathophysiological functions. The knowledge of this family has long been structure-oriented, whereas the structure/function and structure/regulation relationships of the family members and their genes have been largely ignored. These relationships are now being elucidated in events such as gene transcription, precursor processing, changes in plasma protein levels in health and disease and binding capacities that involve hyaluronan as well as other plasma proteins as ligands. This review presents some recent progress made in these fields that paves the way for an understanding of the functions of IαI family members in vivo. Finally, given the wealth of heterogeneous, complicated and sometimes contradictory nomenclatures and acronyms currently in use for this family, a new, uniform, nomenclature is proposed for IαI family genes, precursor polypeptides and assembled proteins.

scholarly journals Flowering in time: genes controlling photoperiodic flowering in Arabidopsis

2001 ◽  
Vol 356 (1415) ◽  
pp. 1761-1767 ◽  
Author(s):  
Jo Putterill
Keyword(s):  
Arabidopsis Thaliana ◽  
Flowering Time ◽  
Recent Progress ◽  
Day Length ◽  
Sharp Transition ◽  
Photoperiodic Flowering ◽  
Expression Of Genes ◽  
Made In ◽  
Transition To Flowering

Successful sexual reproduction in plants relies upon the strict coordination of flowering time with favourable seasons of the year. One of the most important seasonal cues for the model plant Arabidopsis thaliana ( Arabidopsis ) is day length. Genes influencing flowering time in Arabidopsis have been isolated, some of which are involved in the perception and signalling of day length. This review discusses recent progress that has been made in understanding how Arabidopsis integrates environmental and internal signals to ensure a sharp transition to flowering and new insights on the role of the circadian clock in controlling the expression of genes that promote flowering in response to day length.

scholarly journals Coatomer-bound Cdc42 regulates dynein recruitment to COPI vesicles

2005 ◽  
Vol 169 (3) ◽  
pp. 383-389 ◽  
Author(s):  
Ji-Long Chen ◽  
Raymond V. Fucini ◽  
Lynne Lacomis ◽  
Hediye Erdjument-Bromage ◽  
Paul Tempst ◽  
...  
Keyword(s):  
Protein Composition ◽  
Actin Dynamics ◽  
Vesicle Formation ◽  
Binding Interaction ◽  
Temporal Regulation ◽  
Golgi Transport ◽  
Gtp Binding ◽  
Cytoskeletal Dynamics ◽  
Precise Role

Cytoskeletal dynamics at the Golgi apparatus are regulated in part through a binding interaction between the Golgi-vesicle coat protein, coatomer, and the regulatory GTP-binding protein Cdc42 (Wu, W.J., J.W. Erickson, R. Lin, and R.A. Cerione. 2000. Nature. 405:800–804; Fucini, R.V., J.L. Chen, C. Sharma, M.M. Kessels, and M. Stamnes. 2002. Mol. Biol. Cell. 13:621–631). The precise role of this complex has not been determined. We have analyzed the protein composition of Golgi-derived coat protomer I (COPI)–coated vesicles after activating or inhibiting signaling through coatomer-bound Cdc42. We show that Cdc42 has profound effects on the recruitment of dynein to COPI vesicles. Cdc42, when bound to coatomer, inhibits dynein binding to COPI vesicles whereas preventing the coatomer–Cdc42 interaction stimulates dynein binding. Dynein recruitment was found to involve actin dynamics and dynactin. Reclustering of nocodazole-dispersed Golgi stacks and microtubule/dynein-dependent ER-to-Golgi transport are both sensitive to disrupting Cdc42 mediated signaling. By contrast, dynein-independent transport to the Golgi complex is insensitive to mutant Cdc42. We propose a model for how proper temporal regulation of motor-based vesicle translocation could be coupled to the completion of vesicle formation.

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