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Lipid Anchors to Proteins

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Book cover Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

A variety of lipid anchor mechanisms are used to target and stabilise the membrane association of proteins, many of which play important roles in synaptic development, function and plasticity. These lipid anchors include long-chain acyl or prenyl groups, glycosyl-phosphatidylinositol (GPI) and cholesterol. The lipid association with proteins can be either reversible or irreversible and an individual protein may have more than one lipid anchor attached. This chapter summarises some of the main mechanisms of lipid protein anchoring, including myristoylation, palmitoylation, isoprenylation and GPI addition and the enzymes involved in the covalent addition of lipid moieties to proteins. Lipid anchoring can influence protein targeting, especially to membrane lipid rafts, which can have pathological consequences, e.g. in Alzheimer’s disease. Specific examples of lipid-anchored proteins of neurochemical significance will be described in detail, including the prion protein, neural cell adhesion molecules and acetylcholinesterase.

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Abbreviations

AChE:

acetylcholinesterase

ADAM:

A disintegrin and metalloproteinase

AMPA:

α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate

APP:

amyloid precursor protein

BACE:

β-site APP cleaving enzyme (β-secretase)

EGFR:

epidermal growth factor receptor

GAP-43:

Growth Associated Protein 43 (neuromodulin)

GPI:

glycosyl-phosphatidylinositol

HMG:

hydroxymethylglutaryl

MARCKS:

myristoylated alanine-rich C-kinase substrate

MBOAT:

membrane bound O-acyltransferase

N-CAM:

neural cell adhesion molecule

PI-PLC:

phosphatidylinositol specific phospholipase C

PLA2 :

phospholipase A2

PPT:

palmitoyl-protein thioesterase

PRiMA:

proline-rich membrane anchor

PrP:

prion protein

PSD:

post-synaptic density

REP:

rab escort protein

RGGT:

rab geranylgeranyl transferase

Shh:

sonic hedgehog

SNAP:

synaptosome-associated protein

SNARE:

soluble NSF Attachment protein receptors

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Acknowledgments

We thank the UK Medical Research Council, Yorkshire Cancer Research, the Wellcome Trust, the Royal Society and the E.U. INTAS scheme for support of our research.

Authors
  1. N. N. Nalivaeva
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  2. A. J. Turner
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Medical Chemistry, Biochemistry and Biotechnology, Via Saldini 50, 20133, Milan, Italy

    Guido Tettamanti

  3. Department of Internal Medicine Section of Biochemistry, University of Perugia, via del Giochetto, 06122, Perugia, Italy

    Gianfrancesco Goracci

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Nalivaeva, N.N., Turner, A.J. (2009). Lipid Anchors to Proteins. In: Lajtha, A., Tettamanti, G., Goracci, G. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30378-9_14

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