Vps18 deficiency inhibits dendritogenesis in Purkinje cells by blocking the lysosomal degradation of Lysyl Oxidase

Peng, Chao; Yan, Shunfei; Ye, Jian; Shen, Lingxi; Xu, Tian; Tao, Wufan

doi:10.1016/j.bbrc.2012.06.021

Cited by 9 publications

(6 citation statements)

References 25 publications

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“…Recently, 1 study that used lysosomal inhibitors and Vps18-deficient mice demonstrated that LOX protein was degraded through lysosomes in Purkinje cells. 45 However, the detailed molecular mechanisms triggering the degradation of LOX protein have not been reported and should be examined in future studies. Once LOX is cleaved from the proenzyme, it acts as a highly reactive enzyme.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E ₂ Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling

et al. 2014

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E lastic fibers are the largest structures in the extracellular matrix. Beginning with the onset of pulsatile blood flow in the developing aorta and pulmonary artery, smooth muscle cells (SMCs) in the vessel wall produce a complex extracellular matrix that ultimately defines the mechanical properties that are critical for proper function of the neonatal and adult vascular system. 1 As such, hemodynamics and mechanical stress are considered to be the main regulators in the formation of the vascular elastic fiber system during development. 2 Clinical Perspective on p 496The ductus arteriosus (DA) and its connecting elastic arteries (ie, the descending aorta and the main pulmonary trunk) are exposed to essentially the same mechanical forces and hemodynamics. However, since 1914, it has been widely recognized in multiple species that the DA exhibits sparse elastic fibers in the middle layer compared with adjacent elastic arteries, as well as disassembly and fragmentation of the internal elastic lamina. [3][4][5][6][7][8] In the human fetal aorta, newly synthesized uncrosslinked elastin appears at 23 weeks of gestational age to be unevenly distributed on the surface of microfibrils, where it forms continuous strips of variable width. 9 However, the DA exhibits fewer elastic fibers than the aorta. 4,6 This decreased elastogenesis is the hallmark of the vascular remodeling of the DA in humans and a variety of other species. [3][4][5][6][7] It has been suggested that this muscular phenotype of the DA allows it to collapse easily at birth when prostaglandin E 2 (PGE 2 ) is withdrawn and blood flow between the aorta and the pulmonary artery is reduced, thereby permitting immediate postnatal closure of the DA. Conversely, it is known that abnormalities of elastic fibers and elastic lamina are primarily responsible for the persistence of the DA in some human cases.10,11 These abnormalities likely prevent intimal cushion formation and make it difficult to collapse the arterial wall. Therefore, it is Background-Elastic fiber formation begins in mid-gestation and increases dramatically during the last trimester in the great arteries, providing elasticity and thus preventing vascular wall structure collapse. However, the ductus arteriosus (DA), a fetal bypass artery between the aorta and pulmonary artery, exhibits lower levels of elastic fiber formation, which promotes vascular collapse and subsequent closure of the DA after birth. The molecular mechanisms for this inhibited elastogenesis in the DA, which is necessary for the establishment of adult circulation, remain largely unknown. Methods and Results-Stimulation of the prostaglandin E 2 (PGE 2 ) receptor EP4 significantly inhibited elastogenesis and decreased lysyl oxidase (LOX) protein, which catalyzes elastin cross-links in DA smooth muscle cells (SMCs), but not in aortic SMCs. Aortic SMCs expressed much less EP4 than DASMCs. Adenovirus-mediated overexpression of LOX restored the EP4-mediated inhibition of elastogenesis in DASMCs. In EP4-knockout mice, electron microscopi...

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Section: Discussionmentioning

confidence: 99%

Prostaglandin E ₂ Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling

et al. 2014

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“…Defects in lysosomes are common denominators of neuronal diseases and found in, for example, Alzheimer's (Zare-Shahabadi et al, 2015), Parkinson's (Karabiyik et al, 2017) and Huntington's disease (Zhao et al, 2016). Lysosome-associated neurodegeneration is induced by a combination of mechanisms, most importantly, the accumulation of undegraded material (Jiang et al, 2014) and dysregulated signaling (Peng et al, 2012a). These events cause cellular stress and ultimately lead to apoptosis, which is especially damaging in neuronal tissues since these post-mitotic cells have little Aflatounian et al, 2016;Arhan et al, 2009;Bull et al, 2006;Cullinane et al, 2009;Cullinane et al, 2010;Elmeery et al, 2013;Giraud et al, 2017;Gissen et al, 2004;Gissen et al, 2006;Hershkovitz et al, 2008;Huang et al, 2017;Ilhan et al, 2016;Jang et al, 2009;Kim et al, 2011;Li et al, 2014;Moon et al, 2017;Saadah et al, 2013;Sanseverino et al, 2006;Seo et al, 2015;Taha et al, 2007;Tornieri et al, 2013;Wang et al, 2014;Weyand et al, 2016;Zhou and Zhang, 2014 regenerative capacity.…”

Section: Neurological Defectsmentioning

confidence: 99%

CORVET, CHEVI and HOPS – multisubunit tethers of the endo-lysosomal system in health and disease

Beek

Jonker

Welle

et al. 2019

Journal of Cell Science

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Multisubunit tethering complexes (MTCs) are multitasking hubs that form a link between membrane fusion, organelle motility and signaling. CORVET, CHEVI and HOPS are MTCs of the endo-lysosomal system. They regulate the major membrane flows required for endocytosis, lysosome biogenesis, autophagy and phagocytosis. In addition, individual subunits control complex-independent transport of specific cargoes and exert functions beyond tethering, such as attachment to microtubules and SNARE activation. Mutations in CHEVI subunits lead to arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome, while defects in CORVET and, particularly, HOPS are associated with neurodegeneration, pigmentation disorders, liver malfunction and various forms of cancer. Diseases and phenotypes, however, vary per affected subunit and a concise overview of MTC protein function and associated human pathologies is currently lacking. Here, we provide an integrated overview on the cellular functions and pathological defects associated with CORVET, CHEVI or HOPS proteins, both with regard to their complexes and as individual subunits. The combination of these data provides novel insights into how mutations in endo-lysosomal proteins lead to human pathologies.

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“…Similarly, as the genetic deficiency of vacuolar protein sorting protein 18 (VPS18) is reported to facilitate the lysosomal degradation of LOX, the impaired dendritogenesis in VPS18 knockout mice was suggested to be correlated with the accumulation of LOX (52). That study revealed that other than ECM remodeling, LOX may also be capable of regulating organ development.…”

Section: Roles Of Members Of the Lox Family In Organ Developmentmentioning

confidence: 96%

Role of the lysyl oxidase family in organ development (Review)

Wei

Gao

et al. 2020

Exp Ther Med

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Lysyl oxidase proteins (LOXs) are amine oxidases, which are mainly located in smooth muscle cells and fibroblasts and serve an important role in the formation of the extracellular matrix (ECM) in a copper-dependent manner. Owing to the ability of LOX proteins to modulate crosslinking between collagens and to promote the deposition of other fibers, they serve crucially in organogenesis and the subsequent organ development, as well as disease initiation and progression. In addition, ECM formation significantly influences organ morphological formation in both cancer-and non-tumor-related diseases, in addition to cellular epigenetic transformation and migration, under the influence of LOXs. A number of different signaling pathways regulate the LOXs expression and their enzymatic activation. The tissue remodeling and transformation process shares some resemblance between oncogenesis and embryogenesis. Additionally the roles that LOXs serve appeared to be stressed during oncogenesis and tumor metastasis. It has also been indicated LOXs have a noteworthy role in non-tumor diseases. Nonetheless, the role of LOXs in systemic or local organ development and disease control remains unknown. In the present study, the essential roles that LOXs play in embryogenesis were unveiled partially, whereas the role of LOXs in organ or systematic development requires further investigations. The present review aimed to discuss the roles of members of the LOX family in the context of the remodeling of organogenesis and organ development. In addition, the consequences of the malfunction of these proteins related to the development of abnormalities and resulting diseases is discussed. Contents 1. Introduction 2. Roles of members of the LOX family in organ development 3. Signaling pathways involved in the modulation of LOX during tissue development 4. Conclusion Andrology Laboratory and

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Vps18 deficiency inhibits dendritogenesis in Purkinje cells by blocking the lysosomal degradation of Lysyl Oxidase

Cited by 9 publications

References 25 publications

Prostaglandin E ₂ Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling

Prostaglandin E ₂ Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling

CORVET, CHEVI and HOPS – multisubunit tethers of the endo-lysosomal system in health and disease

Role of the lysyl oxidase family in organ development (Review)

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Vps18 deficiency inhibits dendritogenesis in Purkinje cells by blocking the lysosomal degradation of Lysyl Oxidase

Cited by 9 publications

References 25 publications

Prostaglandin E 2 Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling

Prostaglandin E 2 Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling

CORVET, CHEVI and HOPS – multisubunit tethers of the endo-lysosomal system in health and disease

Role of the lysyl oxidase family in organ development (Review)

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Prostaglandin E ₂ Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling

Prostaglandin E ₂ Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling