Logo image
Back
N-myristoylation regulates the axonal distribution of the Fragile X-related protein FXR2P
Journal article   Open access   Peer reviewed

N-myristoylation regulates the axonal distribution of the Fragile X-related protein FXR2P

Emily E. Stackpole, Michael R. Akins and Justin R. Fallon
Molecular and cellular neurosciences, v 62
Sep 2014
DOI: https://doi.org/10.1016/j.mcn.2014.08.003
PMID: 25109237
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc4209718View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Fragile X syndrome FXR2P Myristoylation RNA binding proteins
Fragile X syndrome, the leading cause of inherited intellectual disability and autism, is caused by loss of function of Fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein that regulates local protein synthesis in the somatodendritic compartment. However, emerging evidence also indicates important roles for FMRP in axonal and presynaptic functions. In particular, FMRP and its homologue FXR2P localize axonally and presynaptically to discrete endogenous structures in the brain termed Fragile X granules (FXGs). FXR2P is a component of all FXGs and is necessary for the axonal and presynaptic localization of FMRP to these structures. We therefore sought to identify and characterize structural features of FXR2P that regulate its axonal localization. Sequence analysis reveals that FXR2P harbors a consensus N-terminal myristoylation sequence (MGXXXS) that is absent in FMRP. Using click chemistry with wild type and an unmyristoylatable G2A mutant we demonstrate that FXR2P is N-myristoylated on glycine 2, establishing it as a lipid-modified RNA binding protein. To investigate the role of FXR2P N-myristoylation in neurons we generated fluorescently tagged wild type and unmyristoylatable FXR2P (WT and G2A, respectively) and expressed them in primary cortical cultures. Both FXR2PWT and FXR2PG2A are expressed at equivalent overall levels and are capable of forming FMRP-containing axonal granules. However, FXR2PWT granules are largely restricted to proximal axonal segments while granules formed with unmyristoylatable FXR2PG2A are localized throughout the axonal arbor, including in growth cones. These studies indicate that N-terminal myristoylation of the RNA binding protein FXR2P regulates its localization within the axonal arbor. Moreover, since FMRP localization within axonal domains requires its association with FXR2P, these findings suggest that FXR2P lipid modification is a control point for the axonal and presynaptic distribution of FMRP. •An N-terminal motif directs myristoylation of the RNA binding protein FXR2P.•FXR2P is the only myristoylated member of the Fragile X protein family.•Myristoylation regulates FXR2P granule distribution within axons.

Metrics

4 Record Views
19 citations in Web of Science
18 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#5 Gender Equality

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
Logo image