Regulation of transbilayer plasma membrane phospholipid asymmetry

Daleke, David L.

doi:10.1194/jlr.r200019-jlr200

Cited by 493 publications

(438 citation statements)

References 154 publications

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“…149 Under normal conditions, phospholipid flipping is necessary to maintain lipid asymmetry in the membrane, and is catalyzed by flippase enzymes. 150 Channel forming antibiotics, such as amphotericin B, 151 can enhance phospholipid flipping. Pore-forming peptides, such as GALA and melittin, may also induce flip-flop of phospholipids within the vicinity of the pore.…”

Section: Endosomolysismentioning

confidence: 99%

Intracellular trafficking of nonviral vectors

2005

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Section: Endosomolysismentioning

confidence: 99%

Intracellular trafficking of nonviral vectors

2005

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“…The asymmetric distribution and localization of the aminophospholipid phosphatidylserine (PtdSer) to the cytosolic leaflet of the cellular membrane is actively regulated by the ATPdependent membrane bound aminophospholipid translocase flippase, a P-type ATPase known to transport phospholipids across the bilayer (Daleke, 2003;Paulusma and Oude Elferink, 2005;Tang et al, 1996). In the event asymmetry is altered, PtdSer is exposed to the cell surface, initiating early stages of apoptosis considered crucial to selective recognition and mononuclear phagocytosis of target cells by macrophages and fibroblasts (Castegna et al, 2004;Fadok et al, 2001;Tyurina et al, 2004b).…”

Section: Introductionmentioning

confidence: 99%

Loss of phospholipid asymmetry and elevated brain apoptotic protein levels in subjects with amnestic mild cognitive impairment and Alzheimer disease

Lange

Cenini

Piroddi

et al. 2008

Neurobiology of Disease

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Oxidative stress, a hallmark of Alzheimer disease (AD), has been shown to induce lipid peroxidation and apoptosis disrupting cellular homeostasis. Normally, the aminophospholipid phosphatidylserine (PtdSer) is asymmetrically distributed on the cytosolic leaflet of the lipid bilayer. Under oxidative stress conditions, asymmetry is altered, characterized by the appearance of PtdSer on the outer leaflet, to initiate the first stages of an apoptotic process. PtdSer asymmetry is actively maintained by the ATP-dependent translocase flippase, whose function is inhibited if covalently bound by lipid peroxidation products, 4-hydroxynonenal (HNE) and acrolein, within the membrane bilayer in which they are produced. Additionally, pro-apoptotic proteins Bax and caspase-3 have been implemented in the oxidative modification of PtdSer resulting in subsequent asymmetric collapse, while antiapoptotic protein Bcl-2 has been found to prevent this process.The current investigation focused on detection of PtdSer on the outer leaflet of the bilayer in synaptosomes from brain of subjects with AD and amnestic mild cognitive impairment (MCI), as well as expression levels of apoptosis-related proteins Bcl-2, Bax, and caspase-3. Fluorescence and Western blot analysis suggest PtdSer exposure on the outer leaflet is significantly increased in brain from subjects with MCI and AD contributing to early apoptotic elevation of pro-and anti-apoptotic proteins and finally neuronal loss. MCI is considered a possible transition point between normal cognitive aging and probable AD. Brain from subjects with MCI is reported to have increased levels of tissue oxidation; therefore, the results of this study could mark the progression of patients with MCI into AD. This study contributes to a model of apoptosis-specific oxidation of phospholipids consistent with the notion that PtdSer exposure is required for apoptotic-cell death.

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“…The monomeric CHK proteins combine to form the homo-or hetero-dimeric active forms (15) that catalyze the phosphorylation of choline to phosphocholine in the first committed step in the Kennedy pathway (the cytidine diphosphate (CDP)-choline pathway) for the biosynthesis of phosphatidylcholine (PC) (16). PC is the major phospholipid component of the eukaryotic plasma membrane external leaflet (17), an important precursor for many signaling molecules (18), and is thought to be essential for mammalian survival (19,20). The immediate biosynthetic product of CHK, phosphocholine, may also be an important secondary messenger in regulating cell growth signaling and proliferation (21).…”

mentioning

confidence: 99%

A Rostrocaudal Muscular Dystrophy Caused by a Defect in Choline Kinase Beta, the First Enzyme in Phosphatidylcholine Biosynthesis

Sher

Aoyama

Huebsch

et al. 2006

Journal of Biological Chemistry

110

102

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Muscular dystrophies include a diverse group of genetically heterogeneous disorders that together affect 1 in 2000 births worldwide. The diseases are characterized by progressive muscle weakness and wasting that lead to severe disability and often premature death. Rostrocaudal muscular dystrophy (rmd) is a new recessive mouse mutation that causes a rapidly progressive muscular dystrophy and a neonatal forelimb bone deformity. The rmd mutation is a 1.6-kb intragenic deletion within the choline kinase beta (Chkb) gene, resulting in a complete loss of CHKB protein and enzymatic activity. CHKB is one of two mammalian choline kinase (CHK) enzymes (␣ and ␤) that catalyze the phosphorylation of choline to phosphocholine in the biosynthesis of the major membrane phospholipid phosphatidylcholine. While mutant rmd mice show a dramatic decrease of CHK activity in all tissues, the dystrophy is only evident in skeletal muscle tissues in an unusual rostral-to-caudal gradient. Minor membrane disruption similar to dysferlinopathies suggest that membrane fusion defects may underlie this dystrophy, because severe membrane disruptions are not evident as determined by creatine kinase levels, Evans Blue infiltration, and unaltered levels of proteins in the dystrophin-glycoprotein complex. The rmd mutant mouse offers the first demonstration of a defect in a phospholipid biosynthetic enzyme causing muscular dystrophy, representing a unique model for understanding mechanisms of muscle degeneration.Muscular dystrophies are a variable class of more than 20 human disorders characterized by progressive muscle wasting and weakness resulting from myofiber degeneration and regeneration. Histologically, variation in myofiber size with centrally localized nuclei, fibrosis, and fatty infiltration are common features (1, 2). Despite their common pathologies, the genetic causes, severity, age of onset, and inheritance patterns vary widely among the dystrophies. The Muscular Dystrophy Association currently lists over 40 neuromuscular diseases as targets for its research programs and categorizes them by phenotypic characteristics such as age of onset, affected muscle groups, and inheritance pattern (Muscular Dystrophy Association, www.mdausa.org). In the last 10 years, the genetic mapping and identification of novel skeletal muscle genes, including cytoskeletal, cytosolic, nuclear membrane, sarcolemmal and extracellular matrix proteins, has dramatically changed this phenotype-based classification and provided clues as to the molecular basis of these disorders (3). What was once considered a single disease entity such as limb-girdle muscular dystrophy (LGMD) 4 has now been subdivided into seven different molecularly defined autosomal dominant (LGMD1A-1G) and ten autosomal recessive (LGMD2A-2J) diseases. Not surprisingly, many of these genes have converged to define pathways critical for the normal functioning and maintenance of skeletal muscles. The fact that many muscular dystrophy cases exist in which mutations to known dystrophy-causing genes have...

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Regulation of transbilayer plasma membrane phospholipid asymmetry

Cited by 493 publications

References 154 publications

Intracellular trafficking of nonviral vectors

Intracellular trafficking of nonviral vectors

Loss of phospholipid asymmetry and elevated brain apoptotic protein levels in subjects with amnestic mild cognitive impairment and Alzheimer disease

A Rostrocaudal Muscular Dystrophy Caused by a Defect in Choline Kinase Beta, the First Enzyme in Phosphatidylcholine Biosynthesis

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