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Autophagosome
An autophagosome is a spherical structure with double layer membranes. It is the key structure in macroautophagy, the intracellular degradation system for cytoplasmic contents (e.g., abnormal intracellular proteins, excess or damaged organelles, invading microorganisms). After formation, autophagosomes deliver cytoplasmic components to the lysosomes. The outer membrane of an autophagosome fuses with a lysosome to form an autolysosome. The lysosome's hydrolases degrade the autophagosome-delivered contents and its inner membrane. The formation of autophagosomes is regulated by genes that are well-conserved from yeast to higher eukaryotes. The nomenclature of these genes has differed from paper to paper, but it has been simplified in recent years. The gene families formerly known as APG, AUT, CVT, GSA, PAZ, and PDD are now unified as the ATG (AuTophaGy related) family. The size of autophagosomes vary between mammals and yeast. Yeast autophagosomes are about 500-900 nm, while mam ...
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Macroautophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. It allows the orderly degradation and recycling of cellular components. Although initially characterized as a primordial degradation pathway induced to protect against starvation, it has become increasingly clear that autophagy also plays a major role in the homeostasis of non-starved cells. Defects in autophagy have been linked to various human diseases, including neurodegeneration and cancer, and interest in modulating autophagy as a potential treatment for these diseases has grown rapidly. Four forms of autophagy have been identified: macroautophagy, microautophagy, chaperone-mediated autophagy (CMA), and crinophagy. In macroautophagy (the most thoroughly researched form of autophagy), cytoplasmic components (like mi ...
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Omegasome
] Omegasome is a Cell (biology), cell organelle consisting of lipid bilayer membranes enriched for phosphatidylinositol 3-phosphate (abbreviated PI(3)P or PtdIns3P), and related to a process of autophagy. It is a subdomain of the Endoplasmic Reticulum (ER), and has a morphology resembling the Greek capital letter Omega (Ω). Omegasomes are the sites from which phagophores (also called "isolation membranes") form, which are sack-like structures that mature into autophagosomes, and fuse with lysosomes in order to degrade the contents of the autophagosomes. The formation of omegasomes depends on various factors, however in general, formation of omegasomes is increased as a response to starvation, and in some biochemical situations the presence of PI(3)P leads to the formation of omegasomes. Macroautophagy Autophagy (from Greek words for “self” and “eating”) is a process of digesting or degrading cytoplasmic molecules (proteins, lipids, sugars and organelles). Macroautophagy ...
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ATG8
Autophagy-related protein 8 (Atg8) is a ubiquitin-like protein required for the formation of autophagosomal membranes. The transient conjugation of Atg8 to the autophagosomal membrane through a ubiquitin-like conjugation system is essential for autophagy in eukaryotes. Even though there are homologues in animals (see for example GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B, MAP1LC3B2, and MAP1LC3C), this article mainly focuses on its role in lower eukaryotes such as ''Saccharomyces cerevisiae''. Structure Atg8 is a monomer of 117 aminoacids and a molecular weight of 13,6kDa. It consists of a 5-stranded β-sheet, which is enclosed by two α-helices at one side and one α-helix at the other side and exhibits a conserved GABARAP domain. Even though Atg8 does not show a clear sequence homology to ubiquitin, its crystal structure reveals a conserved ubiquitin-like fold. Function In autophagy Atg8 is one of the key molecular components involved in autophagy, the cellular ...
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Immunocytochemistry
Immunocytochemistry (ICC) is a common laboratory technique that is used to anatomically visualize the localization of a specific protein or antigen in cells by use of a specific primary antibody that binds to it. The primary antibody allows visualization of the protein under a fluorescence microscope when it is bound by a secondary antibody that has a conjugated fluorophore. ICC allows researchers to evaluate whether or not cells in a particular sample express the antigen in question. In cases where an immunopositive signal is found, ICC also allows researchers to determine which sub-cellular compartments are expressing the antigen. Immuno''cyto''chemistry vs. immuno''histo''chemistry Immunocytochemistry differs from immunohistochemistry in that the former is performed on samples of intact cells that have had most, if not all, of their surrounding extracellular matrix removed. This includes individual cells that have been isolated from a block of solid tissue, cells grown with ...
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Huntingtin
Huntingtin (Htt) is the protein coded for in humans by the ''HTT'' gene, also known as the ''IT15'' ("interesting transcript 15") gene. Mutated ''HTT'' is the cause of Huntington's disease (HD), and has been investigated for this role and also for its involvement in long-term memory storage. It is variable in its structure, as the many polymorphisms of the gene can lead to variable numbers of glutamine residues present in the protein. In its wild-type (normal form), it contains 6-35 glutamine residues. However, in individuals affected by Huntington's disease (an autosomal dominant genetic disorder), it contains more than 36 glutamine residues (highest reported repeat length is about 250). Its commonly used name is derived from this disease; previously, the ''IT15'' label was commonly used. The mass of huntingtin protein is dependent largely on the number of glutamine residues it has; the predicted mass is around 350 kDa. Normal huntingtin is generally accepted to be 3144 am ...
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Axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons (pseudounipolar neurons), such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three typesgroup A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. ...
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Neurite
A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before differentiation is complete. Neurite development The development of a neurite requires a complex interplay of both extracellular and intracellular signals. At every given point along a developing neurite, there are receptors detecting both positive and negative growth cues from every direction in the surrounding space. The developing neurite sums together all of these growth signals in order to determine which direction the neurite will ultimately grow towards. While not all of the growth signals are known, several have been identified and characterized. Among the known extracellular growth signals are netrin, a midline chemoattractant, and semaphorin, ephrin and collaps ...
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Neurons
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. Non-animals like plants and fungi do not have nerve cells. Neurons are typically classified into three types based on their function. Sensory neurons respond to stimuli such as touch, sound, or light that affect the cells of the sensory organs, and they send signals to the spinal cord or brain. Motor neurons receive signals from the brain and spinal cord to control everything from muscle contractions to glandular output. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord. When multiple neurons are connected together, they form what is called a neural circuit. A typical neuron consists of a cell body (soma), dendrites, and a single axon. The soma is a compact structure, and the axon and dend ...
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Atg1
AuTophaGy related 1 (Atg1) is a 101.7kDa serine/threonine kinase in ''S.cerevisiae'', encoded by the gene ATG1. It is essential for the initial building of the autophagosome and Cvt vesicles. In a non-kinase role it is - through complex formation with Atg13 and Atg17 - directly controlled by the TOR kinase, a sensor for nutrient availability. Introduction Atg1 can associate with a number of other proteins of the Atg family to form a complex that functions in autophagosome or Cvt vesicle formation. The initiation of autophagy involves the building of the pre-autophagosomal structure (PAS). Most Atg proteins accumulate at the PAS and generate either Cvt vesicles under normal growing conditions or autophagosomes under starvation. To date, there are 31 ATG genes, which can be classified into several different groups according to their functions at the different steps of the pathway. 17 of these genes only work in the Cvt pathway. Structure The Atg1 gene lies on chromosome VII of ...
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Cathepsin D
Cathepsin D is a protein that in humans is encoded by the ''CTSD'' gene. This gene encodes a lysosomal aspartyl protease composed of a protein dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. Cathepsin D is an aspartic endo-protease that is ubiquitously distributed in lysosomes. The main function of cathepsin D is to degrade proteins and activate precursors of bioactive proteins in pre-lysosomal compartments. This proteinase, which is a member of the peptidase A1 family, has a specificity similar to but narrower than that of pepsin A. Transcription of the ''CTSD'' gene is initiated from several sites, including one that is a start site for an estrogen-regulated transcript. Mutations in this gene are involved in the pathogenesis of several diseases, including breast cancer and possibly Alzheimer disease. Homozygous deletion of the ''CTSD'' gene leads to early lethality in the postnatal phase. Deficiency of ''CTSD'' gene has been repo ...
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Endosomes
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation or can be recycled back to the cell membrane in the endocytic cycle. Molecules are also transported to endosomes from the trans Golgi network and either continue to lysosomes or recycle back to the Golgi apparatus. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. Function Endosomes provide an environment for material to be sorted before it reaches the degradative lysosome. For example, low-density lipoprotein (LDL) is taken into the cell by binding to the LDL receptor at the cell surface. Upon reaching early endosomes, the LDL dissociates ...
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MAP1LC3A
Microtubule-associated proteins 1A/1B light chain 3A is a protein that in humans is encoded by the ''MAP1LC3A'' gene. Two transcript variants encoding different isoforms have been found for this gene. Function MAP1A and MAP1B are microtubule-associated proteins which mediate the physical interactions between microtubules and components of the cytoskeleton. MAP1A and MAP1B each consist of a heavy chain subunit and multiple light chain subunits. The protein encoded by this gene is one of the light chain subunits and can associate with either MAP1A or MAP1B. MAPLC3A is one of the mammalian homologues of yeast ATG8, an important marker and effector of autophagy. Regulation MAP1LC3A is regulated by several post-translational modifications. These include covalent linkage of the C-terminus to phosphatidylethanolamine in autophagic membranes, and phosphorylation by protein kinase A, which downregulates its autophagy functions. Noncovalent interactions are important for its car ...
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