scholarly journals ER – lysosome contacts at a pre-axonal region regulate axonal lysosome availability

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nazmiye Özkan ◽  
Max Koppers ◽  
Inge van Soest ◽  
Alexandra van Harten ◽  
Daphne Jurriens ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Neuronal Function ◽  
Organelle Communication

AbstractNeuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the endoplasmic reticulum (ER) and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule – lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule – lysosome contacts at a pre-axonal region finely orchestrate axonal lysosome availability for proper neuronal function.

scholarly journals Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110265
Author(s):  
Vladimir Zhemkov ◽  
Jen Liou ◽  
Ilya Bezprozvanny
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Composition ◽  
Sigma 1 Receptor ◽  
Functional Roles ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Sigma 1 ◽  
Membrane Contact ◽  
Organelle Communication ◽  
Cellular Organelles

Recent studies indicated potential importance of membrane contact sites (MCS) between the endoplasmic reticulum (ER) and other cellular organelles. These MCS have unique protein and lipid composition and serve as hubs for inter-organelle communication and signaling. Despite extensive investigation of MCS protein composition and functional roles, little is known about the process of MCS formation. In this perspective, we propose a hypothesis that MCS are formed not as a result of random interactions between membranes of ER and other organelles but on the basis of pre-existing cholesterol-enriched ER microdomains.

scholarly journals Roles for the Endoplasmic Reticulum in Regulation of Neuronal Calcium Homeostasis

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1232 ◽  
Author(s):  
Nicholas E. Karagas ◽  
Kartik Venkatachalam
Keyword(s):  
Endoplasmic Reticulum ◽  
Neurological Diseases ◽  
Neuronal Function ◽  
Vesicle Release ◽  
Form And Function ◽  
And Function ◽  
Synaptic Vesicle Release ◽  
Activity Dependent ◽  
Ca2 Channels ◽  
Neuronal Compartments

By influencing Ca2+ homeostasis in spatially and architecturally distinct neuronal compartments, the endoplasmic reticulum (ER) illustrates the notion that form and function are intimately related. The contribution of ER to neuronal Ca2+ homeostasis is attributed to the organelle being the largest reservoir of intracellular Ca2+ and having a high density of Ca2+ channels and transporters. As such, ER Ca2+ has incontrovertible roles in the regulation of axodendritic growth and morphology, synaptic vesicle release, and neurotransmission activity dependent gene expression, synaptic plasticity, and mitochondrial bioenergetics. Not surprisingly, many neurological diseases arise from ER Ca2+ dyshomeostasis, either directly due to alterations in ER resident proteins, or indirectly via processes that are coupled to the regulators of ER Ca2+ dynamics. In this review, we describe the mechanisms involved in the establishment of ER Ca2+ homeostasis in neurons. We elaborate upon how changes in the spatiotemporal dynamics of Ca2+ exchange between the ER and other organelles sculpt neuronal function and provide examples that demonstrate the involvement of ER Ca2+ dyshomeostasis in a range of neurological and neurodegenerative diseases.

scholarly journals Post-Translational Modification of Cysteines: A Key Determinant of Endoplasmic Reticulum-Mitochondria Contacts (MERCs)

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110012
Author(s):  
Arthur Bassot ◽  
Junsheng Chen ◽  
Thomas Simmen
Keyword(s):  
Endoplasmic Reticulum ◽  
Redox State ◽  
Oxygen Species ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Catalytic Activation ◽  
Physiological Processes ◽  
Lipid Exchange ◽  
Human Disorders ◽  
Organelle Communication

Cells must adjust their redox state to an ever-changing environment that could otherwise result in compromised homeostasis. An obvious way to adapt to changing redox conditions depends on cysteine post-translational modifications (PTMs) to adapt conformation, localization, interactions and catalytic activation of proteins. Such PTMs should occur preferentially in the proximity of oxidative stress sources. A particular concentration of these sources is found near membranes where the endoplasmic reticulum (ER) and the mitochondria interact on domains called MERCs (Mitochondria-Endoplasmic Reticulum Contacts). Here, fine inter-organelle communication controls metabolic homeostasis. MERCs achieve this goal through fluxes of Ca2+ ions and inter-organellar lipid exchange. Reactive oxygen species (ROS) that cause PTMs of mitochondria-associated membrane (MAM) proteins determine these intertwined MERC functions. Chronic changes of the pattern of these PTMs not only control physiological processes such as the circadian clock but could also lead to or worsen many human disorders such as cancer and neurodegenerative diseases.

scholarly journals ER – lysosome contacts at a pre-axonal region regulate axonal lysosome availability

2020 ◽  
Author(s):  
Nazmiye Özkan ◽  
Max Koppers ◽  
Inge van Soest ◽  
Alexandra van Harten ◽  
Nalan Liv ◽  
...  
Keyword(s):  
Neuronal Function ◽  
Organelle Communication

ABSTRACTNeuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the ER and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule – lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule – lysosome contacts at a pre-axonal region finely orchestrate axonal lysosome availability for proper neuronal function.

scholarly journals Unfolded Protein Response-Dependent Communication and Contact among Endoplasmic Reticulum, Mitochondria, and Plasma Membrane

2018 ◽  
Vol 19 (10) ◽  
pp. 3215 ◽  
Author(s):  
Atsushi Saito ◽  
Kazunori Imaizumi
Keyword(s):  
Endoplasmic Reticulum ◽  
Unfolded Protein Response ◽  
Morphological Changes ◽  
Cellular Damage ◽  
Unfolded Protein ◽  
Contact Sites ◽  
Cellular Events ◽  
Organelle Communication ◽  
The Unfolded Protein Response ◽  
Protein Response

The function of the endoplasmic reticulum (ER) can be impaired by changes to the extra- and intracellular environment, such as disruption of calcium homeostasis, expression of mutated proteins, and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR functions to remove or recover the activity of misfolded proteins that accumulated in the ER and to avoid irreversible cellular damage. Additionally, the UPR plays unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have shown that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication, and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of ER dynamics by the UPR remain unresolved. In this review, we summarize the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

scholarly journals Bidirectional Ca2+ signaling occurs between the endoplasmic reticulum and acidic organelles

2013 ◽  
Vol 200 (6) ◽  
pp. 789-805 ◽  
Author(s):  
Anthony J. Morgan ◽  
Lianne C. Davis ◽  
Siegfried K.T.Y. Wagner ◽  
Alexander M. Lewis ◽  
John Parrington ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Second Messengers ◽  
Ryanodine Receptors ◽  
Lysosomal Function ◽  
Differential Effects ◽  
Organelle Communication ◽  
Oscillations And Waves ◽  
Acidic Organelles

The endoplasmic reticulum (ER) and acidic organelles (endo-lysosomes) act as separate Ca2+ stores that release Ca2+ in response to the second messengers IP3 and cADPR (ER) or NAADP (acidic organelles). Typically, trigger Ca2+ released from acidic organelles by NAADP subsequently recruits IP3 or ryanodine receptors on the ER, an anterograde signal important for amplification and Ca2+ oscillations/waves. We therefore investigated whether the ER can signal back to acidic organelles, using organelle pH as a reporter of NAADP action. We show that Ca2+ released from the ER can activate the NAADP pathway in two ways: first, by stimulating Ca2+-dependent NAADP synthesis; second, by activating NAADP-regulated channels. Moreover, the differential effects of EGTA and BAPTA (slow and fast Ca2+ chelators, respectively) suggest that the acidic organelles are preferentially activated by local microdomains of high Ca2+ at junctions between the ER and acidic organelles. Bidirectional organelle communication may have wider implications for endo-lysosomal function as well as the generation of Ca2+ oscillations and waves.

scholarly journals Unfolded Protein Response-Dependent Communication and Contact among Endoplasmic Reticulum, Mitochondria and Plasma Membrane.

2018 ◽  
Author(s):  
Atsushi Saito ◽  
Kazunori Imaizumi
Keyword(s):  
Endoplasmic Reticulum ◽  
Unfolded Protein Response ◽  
Morphological Changes ◽  
Cellular Damage ◽  
Unfolded Protein ◽  
Contact Sites ◽  
Cellular Events ◽  
Organelle Communication ◽  
The Unfolded Protein Response ◽  
Protein Response

The function of the endoplasmic reticulum (ER) can be impaired by the alternation of the extra- and intracellular environment such as disruption of calcium homeostasis, expression of mutated proteins and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR attempts to recover the protein folding capacity and avoid irreversible cellular damage. Additionally, the UPR has been shown to play unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have indicated that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of its dynamics by UPR remain unresolved. In this review, we summarized the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

scholarly journals In the Right Place at the Right Time: Regulation of Cell Metabolism by IP3R-Mediated Inter-Organelle Ca2+ Fluxes

2021 ◽  
Vol 9 ◽  
Author(s):  
Ulises Ahumada-Castro ◽  
Galdo Bustos ◽  
Eduardo Silva-Pavez ◽  
Andrea Puebla-Huerta ◽  
Alenka Lovy ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Metabolism ◽  
Critical Role ◽  
Degradation Pathways ◽  
Ip3 Receptor ◽  
Organelle Communication ◽  
The Right ◽  
The Relationship ◽  
Synthesis And Degradation

In the last few years, metabolism has been shown to be controlled by cross-organelle communication. The relationship between the endoplasmic reticulum and mitochondria/lysosomes is the most studied; here, inositol 1,4,5-triphosphate (IP3) receptor (IP3R)-mediated calcium (Ca2+) release plays a central role. Recent evidence suggests that IP3R isoforms participate in synthesis and degradation pathways. This minireview will summarize the current findings in this area, emphasizing the critical role of Ca2+ communication on organelle function as well as catabolism and anabolism, particularly in cancer.

IP3R, store-operated Ca2+ entry and neuronal Ca2+ homoeostasis in Drosophila

2012 ◽  
Vol 40 (1) ◽  
pp. 279-281 ◽  
Author(s):  
Sumita Chakraborty ◽  
Gaiti Hasan
Keyword(s):  
Endoplasmic Reticulum ◽  
G Protein Coupled Receptors ◽  
Neuronal Function ◽  
Extracellular Milieu ◽  
Inositol 1,4,5 Trisphosphate ◽  
Membrane Bound ◽  
Trisphosphate Receptor ◽  
Neuronal Physiology ◽  
G Protein Coupled

The IP3R (inositol 1,4,5-trisphosphate receptor) releases Ca2+ from the ER (endoplasmic reticulum) store upon binding to its ligand InsP3, which is thought to be generated by activation of certain membrane-bound G-protein-coupled receptors in Drosophila. Depletion of Ca2+ in the ER store also activates SOCE (store-operated Ca2+ entry) from the extracellular milieu across the plasma membrane, leading to a second rise in cytosolic Ca2+, which is then pumped back into the ER. The role of the IP3R and SOCE in mediating Ca2+ homoeostasis in neurons, their requirement in neuronal function and effect on neuronal physiology and as a consequence behaviour, are reviewed in the present article.

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