In vivo monitoring of the recruitment and activation of AP-1 by Arf1

Sauvageau, Étienne; McCormick, Peter J.; Lefrançois, Stéphane

doi:10.1038/s41598-017-07493-1

Cited by 8 publications

(8 citation statements)

References 40 publications

(47 reference statements)

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“…Additionally, both Arf1 and Arf6 -two small GTPases, which contributed to the recruitment of AP-1A and AP-1B, respectively, in mammalian cells -are found at the plasma membrane, where they regulate endocytosis in both fly and mammalian cells [31,65,[68][69][70][71][72]. Moreover, Arf1 and AP-1 share the localization pattern being present at both TGN and AJs.…”

Section: Discussionmentioning

confidence: 99%

“…Two mammalian isoforms exist, depending on the participant μ subunit: the µ1-containing ubiquitously expressed AP-1A and the µ2-containing epitheliaspecific AP-1B [25][26][27][28]. Although the mammalian μ subunits are 79% identical, AP-1A sorts basolateral cargos at the TGN, where it is recruited by the small GTPase Arf1 [27,[29][30][31] and AP-1B sorts proteins from REs to the basolateral membrane and is regulated by the small GTPase Arf6 (Shteyn et al, 2011). AP-1B is also found at integrin-mediated focal adhesions, and its loss correlates with the migratory behaviour of metastatic cells (Kell et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Multifaceted control of E-cadherin dynamics by the Adaptor Protein Complex 1 during epithelial morphogenesis

Moreno

Boswell

Casbolt

et al. 2021

Preprint

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Intracellular trafficking regulates the distribution of transmembrane proteins including the key determinants of epithelial polarity and adhesion. The Adaptor Protein 1 (AP-1) complex is the key regulator of vesicle sorting, which binds many specific cargos. We examined roles of the AP-1 complex in epithelial morphogenesis, using the Drosophila wing as a paradigm. We found that AP-1 knockdown leads to ectopic tissue folding, which is consistent with the observed defects in integrin targeting to the basal cell-extracellular matrix adhesion sites. This occurs concurrently with an integrin-independent induction of cell death, which counteracts elevated proliferation and prevents hyperplasia. We discovered a distinct pool of AP-1, which localizes at the subapical Adherens Junctions. Upon AP-1 knockdown, E-cadherin is hyperinternalized from these junctions and becomes enriched at the Golgi and recycling endosomes. We then provide evidence that E-cadherin hyperinternalization acts upstream of cell death in a potential tumour-suppressive mechanism. Simultaneously, cells compensate for elevated internalization of E-cadherin by increasing its expression to maintain cell-cell adhesion.Author SummaryThe epithelium is one of the four types of tissues found in animals and is essential for the normal development and maintenance of multicellular organisms. In this tissue, the adhesion protein E-cadherin helps keep cells together and facilitates the coordination of their behaviours. E-cadherin is highly dynamic and undergoes constant turnover by intracellular trafficking machinery. Here, we describe the contributions of one of the core components of intracellular trafficking, the AP-1 complex to E-cadherin dynamics. Using epithelial cells from Drosophila melanogaster, we discover that the AP-1 complex limits E-cadherin internalization from the plasma membrane, which is consistent with the localization of a distinct pool of the AP-1 complex at the sites of E-cadherin cell-cell adhesion. We also show that increased E-cadherin internalization triggers programmed cell death, preventing the tissue from hyperplastic overgrowth in a potential tumour-suppressive mechanism. At the same time, cells compensate for the reduction in the membrane presentation of E-cadherin by increasing its expression, therefore protecting tissue integrity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multifaceted control of E-cadherin dynamics by the Adaptor Protein Complex 1 during epithelial morphogenesis

Moreno

Boswell

Casbolt

et al. 2021

Preprint

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“…Activation of Arf1 for AP-1 recruitment is modulated by BIG2 [ 97 , 98 ], while the GAP implicated in this pathway has not been fully determined. Beyond membrane recruitment, Arf1 activates AP-1 by changing its conformation leading to an increased binding to the cytosolic tail of the sorting receptors [ 99 , 100 ].…”

Section: The Lysosomal Sorting Receptorsmentioning

confidence: 99%

Mechanisms regulating the sorting of soluble lysosomal proteins

2022

Self Cite

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Lysosomes are key regulators of many fundamental cellular processes such as metabolism, autophagy, immune response, cell signalling and plasma membrane repair. These highly dynamic organelles are composed of various membrane and soluble proteins, which are essential for their proper functioning. The soluble proteins include numerous proteases, glycosidases and other hydrolases, along with activators, required for catabolism. The correct sorting of soluble lysosomal proteins is crucial to ensure the proper functioning of lysosomes, and is achieved through the coordinated effort of many sorting receptors, resident ER and Golgi proteins, and several cytosolic components. Mutations in a number of proteins involved in sorting soluble proteins to lysosomes result in human disease. These can range from rare diseases such as lysosome storage disorders, to more prevalent ones, such as Alzheimer’s disease, Parkinson’s disease and others, including rare neurodegenerative diseases that affect children. In this review, we discuss the mechanisms that regulate the sorting of soluble proteins to lysosomes, and highlight the effects of mutations in this pathway that cause human disease. More precisely, we will review the route taken by soluble lysosomal proteins from their translation into the ER, their maturation along the Golgi apparatus, and sorting at the trans-Golgi network. We will also highlight the effects of mutations in this pathway that cause human disease.

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“…COPI; coat protein complex I) and adaptor proteins (e.g. AP1)-promoting vesicle budding from the TGN 379,381 . Arf6 on the other hand, is the predominant Arf isoform localized on the plasma membrane due to a larger positive surface charge, where it may regulate CME via several mechanistic routes 375 .…”

Section: -Arfs Proteins Regulate Distinct Membrane Traffic Processes In a Gtp-dependent Mannermentioning

confidence: 99%

The effects of Mitogenic and Metabolic cues on clathrin-mediated endocytosis

Santos¹

2021

Preprint

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The cell ‘surfaceome’ collectively describes proteins found on the plasma membrane (PM), which functions in fundamental cellular processes including growth and proliferation. The surfaceome undergoes dynamic remodeling via the addition/removal of surface proteins in response to changing environmental conditions. In mammalian cells, surfaceome remodeling is predominantly facilitated by clathrin-mediated endocytosis (CME) which involves the invagination and internalization of PM regions via clathrin-coated structures—removing proteins from the cell surface. As a major regulator of the surfaceome, it is important to understand the underlying mechanisms governing CME, given that its dysregulation has been implicated in human pathologies including neurologic and oncogenic disorders. Cellular cues including mitogenic (e.g. growth factors) and metabolic signals (e.g. cellular energy levels) induce diverse cellular processes (e.g. growth and proliferation) requiring surfaceome/PM remodeling. Precisely how mitogenic and metabolic signals may induce surfaceome remodeling however, is under-examined. As a major regulator of the surfaceome, CME is a likely mechanism through which cellular cues may remodel the PM. Poorly understood, I thus sought to investigate how mitogenic and metabolic signals may regulate CME. Mitogenic signaling by the epidermal growth factor receptor (EGFR) triggers PLCγ1-calcium signals, which I found a requirement for CME of EGFR—likely via calcium control of the Sjn1 protein. Consistently, using TIRF-M imaging coupled to automated software analysis, I demonstrate that inhibition of PLCγ1-calcium signals impairs the formation/assembly of GFR-containing clathrin structures. In addition, I hypothesize that PLCγ1-calcium signals also regulates the CME of other surface proteins given its robust control of Sjn1—which localizes broadly amongst clathrin-coated structures. AMPK is a cellular energy sensor activated by metabolic stress (e.g. starvation). Using TIRF-M imaging coupled to automated software analysis, I found that AMPK activation broadly reduces the formation/assembly of bona fide clathrin-coated pits, without impairing the internalization rates of CME cargoes (e.g. EGFR, TfR and β1-integrin). Furthermore, I found that AMPK may regulate CME throughcontrol of the Arf6 protein. Collectively, my findings uncover and provide novel mechanisms by which mitogenic (via EGFR-induced calcium signals) and metabolic signals (via AMPK control of Arf6) may induce regulation of CME—in eliciting global reorganization of the plasma membrane. 1,2,11–13,3–10

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In vivo monitoring of the recruitment and activation of AP-1 by Arf1

Cited by 8 publications

References 40 publications

Multifaceted control of E-cadherin dynamics by the Adaptor Protein Complex 1 during epithelial morphogenesis

Multifaceted control of E-cadherin dynamics by the Adaptor Protein Complex 1 during epithelial morphogenesis

Mechanisms regulating the sorting of soluble lysosomal proteins

The effects of Mitogenic and Metabolic cues on clathrin-mediated endocytosis

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