Advances in Visualizing and Manipulating Endocytic Trafficking

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 12307

Special Issue Editors


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University of New South Wales (UNSW) Australia, Sydney, Australia

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Guest Editor
School of Medical Science, University of New South Wales, Sydney, Australia

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Guest Editor
University of Otago, Dunedin, Otago, New Zealand

Special Issue Information

Dear Colleagues,

Endocytosis is critical for maintaining the relationship between the extracellular environment and the cellular response. Receptors, ion channels, and adhesion molecules are all dynamically regulated at the plasma membrane by continuous endocytosis and recycling, ensuring the cell responds appropriately to the ions, hormones, lipoproteins and mechanical stimuli presented by the “outside world” of the extracellular environment.

Perturbed endocytic trafficking contributes to a multitude of human diseases, including cardiovascular diseases, neurogenerative disorders and cancer development. Understanding the mechanisms regulating endocytosis is critical to our health, and yet in many ways we are still in the infancy of discovering how endocytic processes are regulated. For example, while clathrin-dependent endocytosis is a well characterized mode of entry into the cell, we are still discovering new endocytic pathways responsible for regulating the uptake of multiple important receptor and circulating proteins. Similarly, our understanding of the endocytic sorting that controls the fate of internalized molecules—whether it is recycled, degraded, and how this is controlled—is also in early stages.

Over recent years, great advances have been made in our ability to directly visualize and manipulate the cell, which is central to our ability to understand endocytic processes. The aim of this Special Issue is to attract original research articles utilizing cutting edge light and electron microscopy techniques to investigate endocytic trafficking, and research articles and reviews focusing on the methodology of manipulating and teasing out the fine detail of endocytic trafficking such as optogenetics, biosensors and fluorescent protein advances. This Special Issue will provide a current summary of the cutting-edge techniques that can be used to understand how endocytosis is regulated, and provide an insight into the future advances that will answer remaining questions surrounding the regulation of endocytic trafficking.

Dr. Nick Ariotti
Dr. Nikita Deo
Dr. Gregory M Redpath
Guest Editors

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Keywords

  • endocytosis
  • endosomal sorting
  • endosomal recycling
  • degradation
  • light microscopy
  • electron microscopy
  • optogenetics
  • fluorescent proteins
  • biosensors

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Published Papers (2 papers)

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Research

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11 pages, 2955 KiB  
Communication
Deficiency of the Lysosomal Protein CLN5 Alters Lysosomal Function and Movement
by Indranil Basak, Rachel A. Hansen, Michael E. Ward and Stephanie M. Hughes
Biomolecules 2021, 11(10), 1412; https://doi.org/10.3390/biom11101412 - 27 Sep 2021
Cited by 13 | Viewed by 3747
Abstract
Batten disease is a devastating, childhood, rare neurodegenerative disease characterised by the rapid deterioration of cognition and movement, leading to death within ten to thirty years of age. One of the thirteen Batten disease forms, CLN5 Batten disease, is caused by mutations in [...] Read more.
Batten disease is a devastating, childhood, rare neurodegenerative disease characterised by the rapid deterioration of cognition and movement, leading to death within ten to thirty years of age. One of the thirteen Batten disease forms, CLN5 Batten disease, is caused by mutations in the CLN5 gene, leading to motor deficits, mental deterioration, cognitive impairment, visual impairment, and epileptic seizures in children. A characteristic pathology in CLN5 Batten disease is the defects in lysosomes, leading to neuronal dysfunction. In this study, we aimed to investigate the lysosomal changes in CLN5-deficient human neurons. We used an induced pluripotent stem cell system, which generates pure human cortical-like glutamatergic neurons. Using CRISPRi, we inhibited the expression of CLN5 in human neurons. The CLN5-deficient human neurons showed reduced acidic organelles and reduced lysosomal enzyme activity measured by microscopy and flow cytometry. Furthermore, the CLN5-deficient human neurons also showed impaired lysosomal movement—a phenotype that has never been reported in CLN5 Batten disease. Lysosomal trafficking is key to maintain local degradation of cellular wastes, especially in long neuronal projections, and our results from the human neuronal model present a key finding to understand the underlying lysosomal pathology in neurodegenerative diseases. Full article
(This article belongs to the Special Issue Advances in Visualizing and Manipulating Endocytic Trafficking)
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Review

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15 pages, 11568 KiB  
Review
Approaches to Visualising Endocytosis of LDL-Related Lipoproteins
by Halima Siddiqui, Nikita Yevstigneyev, Golnoush Madani and Sally McCormick
Biomolecules 2022, 12(2), 158; https://doi.org/10.3390/biom12020158 - 18 Jan 2022
Cited by 12 | Viewed by 8053
Abstract
Endocytosis is the process by which molecules are actively transported into cells. It can take on a variety of forms depending on the cellular machinery involved ranging from specific receptor-mediated endocytosis to the less selective and actin-driven macropinocytosis. The plasma lipoproteins, which deliver [...] Read more.
Endocytosis is the process by which molecules are actively transported into cells. It can take on a variety of forms depending on the cellular machinery involved ranging from specific receptor-mediated endocytosis to the less selective and actin-driven macropinocytosis. The plasma lipoproteins, which deliver lipids and other cargo to cells, have been intensely studied with respect to their endocytic uptake. One of the first molecules to be visualised undergoing endocytosis via a receptor-mediated, clathrin-dependent pathway was low-density lipoprotein (LDL). The LDL molecule has subsequently been shown to be internalised through multiple endocytic pathways. Dissecting the pathways of lipoprotein endocytosis has been crucial to understanding the regulation of plasma lipid levels and how lipids enter cells in the arterial wall to promote atherosclerosis. It has also aided understanding of the dysregulation that occurs in plasma lipid levels when molecules involved in uptake are defective, as is the case in familial hypercholesterolemia (FH). The aim of this review is to outline the many endocytic pathways utilised for lipoprotein uptake. It explores the various experimental approaches that have been applied to visualise lipoprotein endocytosis with an emphasis on LDL and its more complex counterpart, lipoprotein(a) [Lp(a)]. Finally, we look at new developments in lipoprotein visualisation that hold promise for scrutinising endocytic pathways to finer detail in the future. Full article
(This article belongs to the Special Issue Advances in Visualizing and Manipulating Endocytic Trafficking)
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