Dynamin-2 Function and Dysfunction Along the Secretory Pathway

González‐Jamett, Arlek M.; Momboisse, Fanny; Haro-Acuña, Valentina; Bevilacqua, Jorge A.; Caviedes, Pablo; Cárdenas, Ana Marı́a

doi:10.3389/fendo.2013.00126

Cited by 59 publications

(65 citation statements)

References 122 publications

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“…The water fraction was harvested and lyophilized. All heparin derivatives were characterized by onedimensional 13 C NMR to determine the levels of chemical modification.…”

Section: Methodsmentioning

confidence: 99%

“…Different endocytotic pathways are classified according to the specific machinery used, including clathrin-dependent, caveolae-dependent, phagocytotic, marcopinocytotic, and other mechanisms (CLIC/GEECdependent, flotillin-dependent, and Arf6-dependent mechanisms). Some of these processes are mediated by dynamin2, the GTPase involved in both clathrin-mediated endocytosis and caveolae-dependent pathway (11)(12)(13).…”

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confidence: 99%

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Endocytotic Routes of Cobra Cardiotoxins Depend on Spatial Distribution of Positively Charged and Hydrophobic Domains to Target Distinct Types of Sulfated Glycoconjugates on Cell Surface

Lee

Lin

Wang

et al. 2014

Journal of Biological Chemistry

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Background: Cobra venom consists of diverse toxin homologues important for prey capture through variable levels of gene duplication. Results: Comparative structural and cellular investigations revealed sensitivity of toxin homologues for extra-and intracellular targets via sulfated glycoconjugates. Conclusion: Variation in positively charged and hydrophobic domains in CTX homologues altered their target specificities and endocytosis. Significance: We provide a rationale for toxin homologues at cellular level to gain an evolutionary advantage.

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“…The water fraction was harvested and lyophilized. All heparin derivatives were characterized by onedimensional 13 C NMR to determine the levels of chemical modification.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Endocytotic Routes of Cobra Cardiotoxins Depend on Spatial Distribution of Positively Charged and Hydrophobic Domains to Target Distinct Types of Sulfated Glycoconjugates on Cell Surface

Lee

Lin

Wang

et al. 2014

Journal of Biological Chemistry

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“…Glycosylation and further processing of VEGFR2 in the biosynthetic compartments of the ER/Golgi network produces the mature form of 230 kDa (46). Given that interference with regulators of the endocytic routes may also affect transport within the biosynthetic pathway (47)(48)(49)(50), which, consequently, may alter the glycosylation status of VEGFR2, we first tested whether the formation of p130 is due to altered glycosylation of VEGFR2 (e.g. due to lack of glycosylation or deficient carbohydrate processing).…”

Section: Generation Of P130 Is Not Due To Altered Processing In the Bmentioning

confidence: 99%

Constitutive Endocytosis of VEGFR2 Protects the Receptor against Shedding

Basagiannis

Christoforidis

2016

Journal of Biological Chemistry

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VEGFR2 plays a fundamental role in blood vessel formation and in life threatening diseases, such as cancer angiogenesis and cardiovascular disorders. Although inactive growth factor receptors are mainly localized at the plasma membrane, VEGFR2 undergoes constitutive endocytosis (in the absence of ligand) and recycling. Intriguingly, the significance of these futile transport cycles of VEGFR2 remains unclear. Here we found that, unexpectedly, the function of constitutive endocytosis of VEGFR2 is to protect the receptor against plasma membrane cleavage (shedding), thereby preserving the functional state of the receptor until the time of activation by VEGF. Inhibition of constitutive endocytosis of VEGFR2, by interference with the function of clathrin, dynamin, or Rab5, increases dramatically the cleavage/shedding of VEGFR2. Shedding of VEGFR2 produces an N-terminal soluble fragment (100 kDa, s100), which is released in the extracellular space, and a residual C-terminal part (130 kDa, p130) that remains integrated at the plasma membrane. The released soluble fragment (s100) co-immunoprecipitates with VEGF, in line with the topology of the VEGF-binding domain at the N terminus of VEGFR2. Increased shedding of VEGFR2 (via inhibition of constitutive endocytosis) results in reduced response to VEGF, consistently with the loss of the VEGF-binding domain from the membrane remnant of VEGFR2. These data suggest that constitutive internalization of VEGFR2 protects the receptor against shedding and provides evidence for an unprecedented mechanism via which endocytosis can regulate the fate and activity of growth factor receptors.Growth factor receptors are synthesized and processed in the ER/Golgi biosynthetic network. Subsequently, they are delivered to the plasma membrane to become available for binding to their extracellular cognate ligands. In principle, in the absence of ligand, quiescent receptors are preferentially localized at the plasma membrane, whereas only a small percentage of the surface molecules are constitutively internalized (1-3). On the other hand, ligand binding and subsequent receptor activation increases dramatically the efficiency of receptor internalization (3, 4). Internalized receptors explore the different endocytic itineraries and the diverse endocytic compartments to finetune the intensity, nature, and duration of the signaling events (2, 4, 5). Subsequently, growth factor receptors are either recycled back to plasma membrane, for another round of activation, or they are sorted to lysosomes or the proteasome for degradation, leading to irreversible termination of the receptor function (6). In fact, in general, the degradative role of endocytosis is considered to be one of the major housekeeping functions of the cell that eventually down-regulates the levels of the internalized, extracellular or plasma membrane, molecules (7-9).VEGFR2 is a receptor-tyrosine kinase that plays a critical role in blood vessel formation and pathological angiogenesis (10,11). Similarly to other receptor-tyrosine kinas...

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“…Dyn2/Dnm2 has been well‐established as the major membrane pinching and fission protein at the neck of budding clathrin‐coated vesicles at the plasma membrane . Similar to Drp1, Dyn2/Dnm2 molecules form a circular oligomer around the membrane and following GTP hydrolysis, fission is completed .…”

Section: Direct Players In Mitochondrial Fusion and Fissionmentioning

confidence: 90%

Tying trafficking to fusion and fission at the mighty mitochondria

Farmer

Naslavsky

Caplan

2018

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The mitochondrion is a unique organelle that serves as the main site of ATP generation needed for energy in the cell. However, mitochondria also play essential roles in cell death through apoptosis and necrosis, as well as a variety of crucial functions related to stress regulation, autophagy, lipid synthesis and calcium storage. There is a growing appreciation that mitochondrial function is regulated by the dynamics of its membrane fusion and fission; longer, fused mitochondria are optimal for ATP generation, whereas fission of mitochondria facilitates mitophagy and cell division. Despite the significance of mitochondrial homeostasis for such crucial cellular events, the intricate regulation of mitochondrial fusion and fission is only partially understood. Until very recently, only a single mitochondrial fission protein had been identified. Moreover, only now have researchers turned to address the upstream machinery that regulates mitochondrial fusion and fission proteins. Herein, we review the known GTPases involved in mitochondrial fusion and fission, but also highlight recent studies that address the mechanisms by which these GTPases are regulated. In particular, we draw attention to a substantial new body of literature linking endocytic regulatory proteins, such as the retromer VPS35 cargo selection complex subunit, to mitochondrial homeostasis. These recent studies suggest that relationships and cross-regulation between endocytic and mitochondrial pathways may be more widespread than previously assumed.

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Dynamin-2 Function and Dysfunction Along the Secretory Pathway

Cited by 59 publications

References 122 publications

Endocytotic Routes of Cobra Cardiotoxins Depend on Spatial Distribution of Positively Charged and Hydrophobic Domains to Target Distinct Types of Sulfated Glycoconjugates on Cell Surface

Endocytotic Routes of Cobra Cardiotoxins Depend on Spatial Distribution of Positively Charged and Hydrophobic Domains to Target Distinct Types of Sulfated Glycoconjugates on Cell Surface

Constitutive Endocytosis of VEGFR2 Protects the Receptor against Shedding

Tying trafficking to fusion and fission at the mighty mitochondria

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