XLMR protein related to neurite extension (Xpn/KIAA2022) regulates cell-cell and cell-matrix adhesion and migration.
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.
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, University of Fukui, Japan.
Takuya
T
Magome
Department of Molecular Neuropsychiatry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan. Electronic address: hattori@anat2.med.osaka-u.ac.jp.
Tsuyoshi
T
Hattori
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan.
Manabu
M
Taniguchi
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, University of Fukui, Japan.
Toshiko
T
Ishikawa
Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka, Japan.
Shingo
S
Miyata
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, University of Fukui, Japan.
Kohei
K
Yamada
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, University of Fukui, Japan.
Hironori
H
Takamura
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, University of Fukui, Japan; Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan.
Shinsuke
S
Matsuzaki
Department of Molecular Neuropsychiatry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan.
Akira
A
Ito
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, University of Fukui, Japan; Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan; Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka, Japan.
Masaya
M
Tohyama
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, University of Fukui, Japan.
Taiichi
T
Katayama
D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics* / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology*; D000089662:Doublecortin Protein; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D014945:Wound Healing / Q000235:genetics
D015820:Cadherins; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; C000598871:NEXMIF protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering
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