Research Summary: CXCR7 Protein Expression in Human Adult Brain and Differentiated Neurons



CXCR7 and CXCR4 are receptors for the chemokine CXCL12, which is involved in
essential functions of the immune and nervous systems. Although
CXCR7 transcripts are widely expressed throughout the
central nervous system, little is known about its protein distribution and
function in the adult brain. To evaluate its potential involvement in
CXCL12/CXCR4 signaling in differentiated neurons, we studied CXCR7 protein
expression in human brain and cultured neurons.

Methodology/Principal Findings

Immunohistochemistry and RT-PCR analyses of cortex and hippocampus from
control and HIV-positive subjects provided the first evidence of CXCR7
protein expression in human adult neurons, under normal and pathological
conditions. Furthermore, confocal microscopy and binding assays in cultured
neurons show that CXCR7 protein is mainly located into cytoplasm, while
little to no protein expression is found on neuronal plasma membrane.
Interestingly, specific CXCR7 ligands that inhibit CXCL12 binding to CXCR7
do not alter CXCR4-activated survival signaling (pERK/pAkt) in rat cortical
neurons. Neuronal CXCR7 co-localizes to some extent with the endoplasmic
reticulum marker ERp29, but not with early/late endosome markers.
Additionally, large areas of overlap are detected in the intracellular
pattern of CXCR7 and CXCR4 expression.


Overall, these results implicate CXCR4 as the main CXCL12 signaling receptor
on the surface of differentiated neurons and suggest that CXCR7 may interact
with CXCR4 at the intracellular level, possibly affecting CXCR4 trafficking
and/or coupling to other proteins.


Publisher: Public Library of Science

Date Published: 31-May-2011

Author(s): Shimizu S., Brown M., Sengupta R., Penfold M., Meucci O.


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