XLMR protein related to neurite extension (Xpn/KIAA2022) regulates cell-cell and cell-matrix adhesion and migration

Abstract

X-linked mental retardation (XLMR) is a common cause of moderate to severe intellectual disability in males. XLMR protein related to neurite extension (Xpn, also known as KIAA2022) has been implicated as a gene responsible for XLMR in humans. Although Xpn is highly expressed in the developing brain and is involved in neurite outgrowth in PC12 cells and neurons, little is known about the functional role of Xpn. Here, we show that Xpn regulates cell-cell and cell-matrix adhesion and migration in PC12 cells. Xpn knockdown enhanced cell-cell and cell-matrix adhesion mediated by N-cadherin and β1-integrin, respectively. N-Cadherin and β1-integrin expression at the mRNA and protein levels was significantly increased in Xpn knockdown PC12 cells. Furthermore, overexpressed Xpn protein was strongly expressed in the nuclei of PC12 and 293T cells. Finally, depletion of Xpn perturbed cellular migration by enhancing N-cadherin and β1-integrin expression in a PC12 cell wound healing assay. We conclude that Xpn regulates cell-cell and cell-matrix adhesion and cellular migration by regulating the expression of adhesion molecules.

Keywords: 6-diamidino-2-phenylindole dihydrochloride; ARX; ATRX; CP; DAPI; DCX; GAPDH; GFP; KIAA2022; Migration; N-Cadherin; NGF; RFP; TUBA1A; VLDLR; X-linked mental retardation; XLMR; XLMR protein related to neurite extension; Xpn; alpha thalassemia/mental retardation syndrome X-linked; aristaless related homeobox; cortical plate; doublecortin; glyceraldehyde 3-phosphate dehydrogenase; green fluorescent protein; nerve growth factor; qRT-PCR; quantitative real-time PCR; red fluorescent protein; tubulin alpha1A; very low density lipoprotein receptor; β1-Integrin.