Palmitoylation and Membrane Binding of Arc/Arg3.1: A Potential Role in Synaptic Depression

Barbara Barylko, Julia R. Wilkerson, Sheridan H. Cavalier, Derk D. Binns, Nicholas G. James, David M. Jameson, Kimberly M. Huber, Joseph P. Albanesi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Activity-regulated cytoskeletal-associated protein (Arc, also known as activity-regulated gene 3.1 or Arg3.1) is induced in neurons in response to salient experience and neural activity and is necessary for activity-induced forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), cellular substrates of learning and memory. The best-characterized function of Arc is enhancement of the endocytic internalization of AMPA receptors in dendritic spines, a process associated with LTD. Arc has also been implicated in the proteolytic processing of amyloid precursor protein on the surface of endosomes. To mediate these activities, Arc must associate with cellular membranes, but it is unclear whether Arc binds directly to the lipid bilayer or requires protein-protein interactions for membrane recruitment. In this study, we show that Arc associates with pure phospholipid vesicles in vitro and undergoes palmitoylation in neurons, a modification that allows it to insert directly into the hydrophobic core of the bilayer. The palmitoylated cysteines are clustered in a motif, 94CLCRC98, located in the N-terminal half of the protein, which has not yet been structurally characterized. Expression of Arc with three mutated cysteines in that motif cannot support synaptic depression induced by the activity-dependent transcription factor, MEF2 (myocyte enhancer factor 2), in contrast to wild-type Arc. Thus, it appears that palmitoylation regulates at least a subset of Arc functions in synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)520-524
Number of pages5
JournalBiochemistry
Volume57
Issue number5
DOIs
StatePublished - Feb 6 2018

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Lipoylation
Neuronal Plasticity
Cysteine
MEF2 Transcription Factors
Depression
Membranes
Neurons
Dendritic Spines
AMPA Receptors
Plasticity
Long-Term Potentiation
Amyloid beta-Protein Precursor
Endosomes
Lipid Bilayers
Phospholipids
Membrane Proteins
Proteins
Lipid bilayers
Transcription Factors
Learning

ASJC Scopus subject areas

  • Biochemistry

Cite this

Palmitoylation and Membrane Binding of Arc/Arg3.1 : A Potential Role in Synaptic Depression. / Barylko, Barbara; Wilkerson, Julia R.; Cavalier, Sheridan H.; Binns, Derk D.; James, Nicholas G.; Jameson, David M.; Huber, Kimberly M.; Albanesi, Joseph P.

In: Biochemistry, Vol. 57, No. 5, 06.02.2018, p. 520-524.

Research output: Contribution to journalArticle

Barylko, Barbara ; Wilkerson, Julia R. ; Cavalier, Sheridan H. ; Binns, Derk D. ; James, Nicholas G. ; Jameson, David M. ; Huber, Kimberly M. ; Albanesi, Joseph P. / Palmitoylation and Membrane Binding of Arc/Arg3.1 : A Potential Role in Synaptic Depression. In: Biochemistry. 2018 ; Vol. 57, No. 5. pp. 520-524.
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