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Trends in Cardiovascular Medicine Jul 2015Cardiomyocytes, the individual contractile units of heart muscle, are long-lived and robust. Given the longevity of these cells, it can be easy to overlook their dynamic... (Review)
Review
Cardiomyocytes, the individual contractile units of heart muscle, are long-lived and robust. Given the longevity of these cells, it can be easy to overlook their dynamic intracellular environment that contain rapid protein movements and frequent protein turnover. Critical gene transcription and protein translation occur continuously, as well as trafficking and localization of proteins to specific functional zones of cell membrane. As heart failure becomes an increasingly important clinical entity, growing numbers of investigative teams are examining the cell biology of healthy and diseased cardiomyocytes. In this review, we introduce the major architectural structures and types of protein movements within cardiac cells, and then review recent studies that explore the regulation of such movements. We conclude by introducing current translational directions of the basic studies with a focus on novel areas of therapeutic development.
Topics: Heart Failure; Humans; Myocytes, Cardiac; Protein Transport
PubMed: 25649302
DOI: 10.1016/j.tcm.2014.12.012 -
Plant Physiology Apr 2021Membranes are essential for cells and organelles to function. As membranes are impermeable to most polar and charged molecules, they provide electrochemical energy to...
Membranes are essential for cells and organelles to function. As membranes are impermeable to most polar and charged molecules, they provide electrochemical energy to transport molecules across and create compartmentalized microenvironments for specific enzymatic and cellular processes. Membranes are also responsible for guided transport of cargoes between organelles and during endo- and exocytosis. In addition, membranes play key roles in cell signaling by hosting receptors and signal transducers and as substrates and products of lipid second messengers. Anionic lipids and their specific interaction with target proteins play an essential role in these processes, which are facilitated by specific lipid-binding domains. Protein crystallography, lipid-binding studies, subcellular localization analyses, and computer modeling have greatly advanced our knowledge over the years of how these domains achieve precision binding and what their function is in signaling and membrane trafficking, as well as in plant development and stress acclimation.
Topics: Biological Transport, Active; Cell Membrane; Lipid Metabolism; Plant Physiological Phenomena; Protein Transport; Signal Transduction
PubMed: 33793907
DOI: 10.1093/plphys/kiaa100 -
Neuroscience Letters Nov 2021This mini-review aims to summarize a growing body of literature on synaptojanin 1 (Synj1), a phosphoinositide phosphatase that was initially known to have a prominent... (Review)
Review
This mini-review aims to summarize a growing body of literature on synaptojanin 1 (Synj1), a phosphoinositide phosphatase that was initially known to have a prominent role in synaptic vesicle recycling. Synj1 is coded by the SYNJ1 gene, whose mutations and variants are associated with an increasing number of neurological disorders. To better understand the mechanistic role of Synj1 in disease pathogenesis, we review details of phosphoinositide signaling pathways and the reported involvement of Synj1 in membrane trafficking with a specific focus on Parkinson's disease (PD). Recent studies have tremendously advanced our understanding of Synj1 protein structure and function while broadening our view of how Synj1 regulates synaptic membrane trafficking and endosomal trafficking in various organisms and cell types. A growing body of evidence points to inefficient membrane trafficking as key pathogenic mechanisms in neurodegenerative diseases associated with abnormal Synj1 expression. Despite significant progress made in the field, the mechanism by which Synj1 connects to trafficking, signaling, and pathogenesis is lacking and remains to be addressed.
Topics: Animals; Humans; Nerve Tissue Proteins; Neurodegenerative Diseases; Phosphoric Monoester Hydrolases; Protein Transport
PubMed: 34637856
DOI: 10.1016/j.neulet.2021.136288 -
Progress in Retinal and Eye Research Sep 2013Vision is the most fundamental of our senses initiated when photons are absorbed by the rod and cone photoreceptor neurons of the retina. At the distal end of each... (Review)
Review
Vision is the most fundamental of our senses initiated when photons are absorbed by the rod and cone photoreceptor neurons of the retina. At the distal end of each photoreceptor resides a light-sensing organelle, called the outer segment, which is a modified primary cilium highly enriched with proteins involved in visual signal transduction. At the proximal end, each photoreceptor has a synaptic terminal, which connects this cell to the downstream neurons for further processing of the visual information. Understanding the mechanisms involved in creating and maintaining functional compartmentalization of photoreceptor cells remains among the most fascinating topics in ocular cell biology. This review will discuss how photoreceptor compartmentalization is supported by protein sorting, targeting and trafficking, with an emphasis on the best-studied cases of outer segment-resident proteins.
Topics: Animals; Humans; Photoreceptor Cells, Vertebrate; Protein Transport
PubMed: 23562855
DOI: 10.1016/j.preteyeres.2013.03.002 -
Trends in Microbiology Jul 2020In the evolutionary arms race between pathogens and plants, pathogens evolved effector molecules that they secrete into the host to subvert plant cellular responses in a... (Review)
Review
In the evolutionary arms race between pathogens and plants, pathogens evolved effector molecules that they secrete into the host to subvert plant cellular responses in a process termed the effector-targeted pathway (ETP). During recent years the repertoire of ETPs has increased and mounting evidence indicates that the proteasome and autophagy pathways are central hubs of microbial effectors. Both degradation pathways are implicated in a broad array of cellular responses and thus constitute an attractive target for effector proteins to have a broader impact on the host. In this article we first summarize recent findings on how effectors from various pathogens modulate proteolytic pathways and then provide a network analysis of established effector targets implicated in proteolytic degradation machineries. With this network we emphasize the idea that effectors targeting proteolytic degradation pathways will affect the protein synthesis-transport and degradation triangle. We put in perspective that, in utilizing the effector diversity of microbes, we produce excellent tools to study diverse cellular pathways and their possible interplay with each other.
Topics: Autophagy; Host-Pathogen Interactions; Peptide Hydrolases; Plant Diseases; Plants; Protein Transport; Proteolysis
PubMed: 32544439
DOI: 10.1016/j.tim.2020.02.010 -
Open Biology Aug 2023Encapsulation and compartmentalization are fundamental to the evolution of cellular life, but they also pose a challenge: how to partition the molecules that perform... (Review)
Review
Encapsulation and compartmentalization are fundamental to the evolution of cellular life, but they also pose a challenge: how to partition the molecules that perform biological functions-the proteins-across impermeable barriers into sub-cellular organelles, and to the outside. The solution lies in the evolution of specialized machines, translocons, found in every biological membrane, which act both as gate and gatekeeper across and into membrane bilayers. Understanding how these translocons operate at the molecular level has been a long-standing ambition of cell biology, and one that is approaching its denouement; particularly in the case of the ubiquitous Sec system. In this review, we highlight the fruits of recent game-changing technical innovations in structural biology, biophysics and biochemistry to present a largely complete mechanism for the bacterial version of the core Sec machinery. We discuss the merits of our model over alternative proposals and identify the remaining open questions. The template laid out by the study of the Sec system will be of immense value for probing the many other translocons found in diverse biological membranes, towards the ultimate goal of altering or impeding their functions for pharmaceutical or biotechnological purposes.
Topics: Protein Transport; Cell Membrane
PubMed: 37643640
DOI: 10.1098/rsob.230166 -
Molecular Neurodegeneration Aug 2014Intracellular protein trafficking plays an important role in neuronal function and survival. Protein misfolding is a common theme found in many neurodegenerative... (Review)
Review
Intracellular protein trafficking plays an important role in neuronal function and survival. Protein misfolding is a common theme found in many neurodegenerative diseases, and intracellular trafficking machinery contributes to the pathological accumulation and clearance of misfolded proteins. Although neurodegenerative diseases exhibit distinct pathological features, abnormal endocytic trafficking is apparent in several neurodegenerative diseases, such as Alzheimer's disease (AD), Down syndrome (DS) and Parkinson's disease (PD). In this review, we will focus on protein sorting defects in three major neurodegenerative diseases, including AD, DS and PD. An important pathological feature of AD is the presence of extracellular senile plaques in the brain. Senile plaques are composed of β-amyloid (Aβ) peptide aggregates. Multiple lines of evidence demonstrate that over-production/aggregation of Aβ in the brain is a primary cause of AD and attenuation of Aβ generation has become a topic of extreme interest in AD research. Aβ is generated from β-amyloid precursor protein (APP) through sequential cleavage by β-secretase and the γ-secretase complex. Alternatively, APP can be cleaved by α-secretase within the Aβ domain to release soluble APPα which precludes Aβ generation. DS patients display a strikingly similar pathology to AD patients, including the generation of neuronal amyloid plaques. Moreover, all DS patients develop an AD-like neuropathology by their 40 s. Therefore, understanding the metabolism/processing of APP and how these underlying mechanisms may be pathologically compromised is crucial for future AD and DS therapeutic strategies. Evidence accumulated thus far reveals that synaptic vesicle regulation, endocytic trafficking, and lysosome-mediated autophagy are involved in increased susceptibility to PD. Here we review current knowledge of endosomal trafficking regulation in AD, DS and PD.
Topics: Animals; Humans; Nerve Degeneration; Neurodegenerative Diseases; Protein Transport
PubMed: 25152012
DOI: 10.1186/1750-1326-9-31 -
Aging Apr 2018
Topics: Animals; Humans; Protein Folding; Protein Transport
PubMed: 29706613
DOI: 10.18632/aging.101435 -
Bioarchitecture 2015The neural cell adhesion molecule (NCAM) regulates differentiation and functioning of neurons by accumulating at the cell surface where it mediates the interactions of... (Review)
Review
The neural cell adhesion molecule (NCAM) regulates differentiation and functioning of neurons by accumulating at the cell surface where it mediates the interactions of neurons with the extracellular environment. NCAM also induces a number of intracellular signaling cascades, which coordinate interactions at the cell surface with intracellular processes including changes in gene expression, transport and cytoskeleton remodeling. Since NCAM functions at the cell surface, its transport and delivery to the cell surface play a critical role. Here, we review recent advances in our understanding of the molecular mechanisms of the intracellular transport and cell surface delivery of NCAM. We also discuss the data suggesting a possibility of cross talk between activation of NCAM at the cell surface and the intracellular transport and cell surface delivery of NCAM.
Topics: Animals; Humans; Neural Cell Adhesion Molecules; Neurons; Protein Transport; Receptor Cross-Talk
PubMed: 26605672
DOI: 10.1080/19490992.2015.1118194 -
Journal of the American Society of... Jul 2014Renal epithelial cells must maintain distinct protein compositions in their apical and basolateral membranes in order to perform their transport functions. The creation... (Review)
Review
Renal epithelial cells must maintain distinct protein compositions in their apical and basolateral membranes in order to perform their transport functions. The creation of these polarized protein distributions depends on sorting signals that designate the trafficking route and site of ultimate functional residence for each protein. Segregation of newly synthesized apical and basolateral proteins into distinct carrier vesicles can occur at the trans-Golgi network, recycling endosomes, or a growing assortment of stations along the cellular trafficking pathway. The nature of the specific sorting signal and the mechanism through which it is interpreted can influence the route a protein takes through the cell. Cell type-specific variations in the targeting motifs of a protein, as are evident for Na,K-ATPase, demonstrate a remarkable capacity to adapt sorting pathways to different developmental states or physiologic requirements. This review summarizes our current understanding of apical and basolateral trafficking routes in polarized epithelial cells.
Topics: Cell Polarity; Endosomes; Epithelial Cells; Kidney; Protein Transport; Urothelium
PubMed: 24652803
DOI: 10.1681/ASN.2013080883