Intracellular Phospholipase A1γ (iPLA1γ) Is a Novel Factor Involved in Coat Protein Complex I- and Rab6-independent Retrograde Transport between the Endoplasmic Reticulum and the Golgi Complex

Morikawa, Rei; Aoki, Junken; Kano, Fumi; Murata, Masayuki; Yamamoto, Akira; Tsujimoto, Masafumi; Arai, Hiroyuki

doi:10.1074/jbc.m109.038869

Cited by 47 publications

(55 citation statements)

References 60 publications

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“…RNA-interference experiments in cellular systems indicated a role of DDHD2 in transport from the Golgi to the plasma membrane. In view of this, it was hypothesized that DDHD2 facilitates membrane and vesicle fusion by the modification of membranes through phospholipid hydrolysis (Inoue et al, 2012;Morikawa et al, 2009;Nakajima et al, 2002;Sato et al, 2010;Tani et al, 1999).…”

Section: Spg54mentioning

confidence: 99%

Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms

Giudice

Lombardi

Santorelli

et al. 2014

Experimental Neurology

294

278

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Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurological disorders characterized by pathophysiologic hallmark of length-dependent distal axonal degeneration of the corticospinal tracts. The prominent features of this pathological condition are progressive spasticity and weakness of the lower limbs. To date, 72 spastic gait disease-loci and 55 spastic paraplegia genes (SPGs) have been identified. All modes of inheritance (autosomal dominant, autosomal recessive, and X-linked) have been described. Recently, a late onset spastic gait disorder with maternal trait of inheritance has been reported, as well as mutations in genes not yet classified as spastic gait disease. Several cellular processes are involved in its pathogenesis, such as membrane and axonal transport, endoplasmic reticulum membrane modeling and shaping, mitochondrial function, DNA repair, autophagy, and abnormalities in lipid metabolism and myelination processes. Moreover, recent evidences have been found about the impairment of endosome membrane trafficking in vesicle formation and about the involvement of oxidative stress and mtDNA polymorphisms in the onset of the disease. Interactome networks have been postulated by bioinformatics and biological analyses of spastic paraplegia genes, which would contribute to the development of new therapeutic approaches.

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Section: Spg54mentioning

confidence: 99%

Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms

Giudice

Lombardi

Santorelli

et al. 2014

Experimental Neurology

294

278

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“…DDHD2 is ubiquitously expressed; a cytosolic and a membrane-associated pool, localizing to the cis-Golgi and the ER-Golgi intermediate compartment (ERGIC) are in a dynamic equilibrium. [11][12][13] Overexpression of DDHD2 leads to dispersion of the Golgi and enlargement of the perinuclear ERGIC. 12,14 Conflicting data exists about the effect of DDHD2 depletion.…”

Section: Discussionmentioning

confidence: 99%

Mutations in phospholipase DDHD2 cause autosomal recessive hereditary spastic paraplegia (SPG54)

et al. 2013

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Hereditary spastic paraplegias (HSP) are a genetically heterogeneous group of disorders characterized by a distal axonopathy of the corticospinal tract motor neurons leading to progressive lower limb spasticity and weakness. Intracellular membrane trafficking, mitochondrial dysfunction and myelin formation are key functions involved in HSP pathogenesis. Only recently defects in metabolism of complex lipids have been implicated in a number of HSP subtypes. Mutations in the 23 known autosomal recessive HSP genes explain less than half of autosomal recessive HSP cases. To identify novel autosomal recessive HSP disease genes, exome sequencing was performed in 79 index cases with autosomal recessive forms of HSP. Resulting variants were filtered and intersected between families to allow identification of new disease genes. We identified two deleterious mutations in the phospholipase DDHD2 gene in two families with complicated HSP. The phenotype is characterized by early onset of spastic paraplegia, mental retardation, short stature and dysgenesis of the corpus callosum. Phospholipase DDHD2 is involved in intracellular membrane trafficking at the golgi/ endoplasmic reticulum interface and has been shown to possess phospholipase A1 activity in vitro. Discovery of DDHD2 mutations in HSP might therefore provide a link between two key pathogenic themes in HSP: membrane trafficking and lipid metabolism.

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“…The enzymatic machinery that regulates membrane lipids in compartments of the secretory pathway determines their morphology, associated membrane trafficking and lipid-protein interaction (Bechler et al, 2010;Ben-Tekaya et al, 2010;Brown et al, 2003;de Figueiredo et al, 2000;Morikawa et al, 2009;San Pietro et al, 2009;Schmidt and Brown, 2009;Subathra et al, 2011). Here we incorporate LPP3 into the enzymatic machinery (PLD, SMS, LPAAT3, and PLA 2 ) already related to the generation of the DAG necessary for the transport carrier formation along the secretory pathway.…”

Section: Lpp3 Metabolizes Lipids Involved In Early Secretory Membranementioning

confidence: 99%

Lipid phosphate phosphatase 3 participates in transport carrier formation and protein trafficking in the early secretory pathway

Gutiérrez-Martínez

Fernández-Ulibarri

Lázaro‐Diéguez

et al. 2013

Journal of Cell Science

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SummaryThe inhibition of phosphatidic acid phosphatase (PAP) activity by propanolol indicates that diacylglycerol (DAG) is required for the formation of transport carriers at the Golgi and for retrograde trafficking to the ER. Here we report that the PAP2 family member lipid phosphate phosphatase 3 (LPP3, also known as PAP2b) localizes in compartments of the secretory pathway from ER export sites to the Golgi complex. The depletion of human LPP3: (i) reduces the number of tubules generated from the ER-Golgi intermediate compartment and the Golgi, with those formed from the Golgi being longer in LPP3-silenced cells than in control cells; (ii) impairs the Rab6-dependent retrograde transport of Shiga toxin subunit B from the Golgi to the ER, but not the anterograde transport of VSV-G or ssDsRed; and (iii) induces a high accumulation of Golgi-associated membrane buds. LPP3 depletion also reduces levels of de novo synthesized DAG and the Golgi-associated DAG contents. Remarkably, overexpression of a catalytically inactive form of LPP3 mimics the effects of LPP3 knockdown on Rab6-dependent retrograde transport. We conclude that LPP3 participates in the formation of retrograde transport carriers at the ER-Golgi interface, where it transitorily cycles, and during its route to the plasma membrane.

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Intracellular Phospholipase A1γ (iPLA1γ) Is a Novel Factor Involved in Coat Protein Complex I- and Rab6-independent Retrograde Transport between the Endoplasmic Reticulum and the Golgi Complex

Cited by 47 publications

References 60 publications

Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms

Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms

Mutations in phospholipase DDHD2 cause autosomal recessive hereditary spastic paraplegia (SPG54)

Lipid phosphate phosphatase 3 participates in transport carrier formation and protein trafficking in the early secretory pathway

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