Amyloid precursor like protein-1 promotes JNK-mediated cell migration in Drosophila.

Xingjun Wang,Lingzhi Kong,Shilong Han,Wenzhe Li,Ying Sun,Yeqing Ma,Yu Zhao,Yujun Chen,Fan Zhang,Yingyao Shao,Chenxi Wu,Lei Xue

doi:10.18632/oncotarget.17681

Abstract

The amyloid precursor like protein-1 (APLP1) is a member of the amyloid precursor protein (APP) family in mammals. While many studies have been focused on the pathologic role of APP in Alzheimer's disease, the physiological functions of APLP1 have remained largely elusive. Here we report that ectopic expression of APLP1 in Drosophila induces cell migration, which is suppressed by the loss of JNK signaling and enhanced by the gain of JNK signaling. APLP1 activates JNK signaling through phosphorylation of JNK, which up-regulates the expression of matrix metalloproteinase MMP1 required for basement membranes degradation and promotes actin remodeling essential for cell migration. Our data thus provide the first in vivo evidence for a cell-autonomous role of APLP1 protein in migration.

Highlights

Amyloid precursor-like protein 1 (APLP1) is a member of the highly conserved amyloid precursor protein family that includes amyloid precursor protein (APP) and amyloid precursor-like protein 2 (APLP2) in mammals [1,2,3,4]
This phenotype was further enhanced by adding another copy of UAS-amyloid precursor like protein-1 (APLP1) (Figures 1c and 1c’), as the number of discs showing strong migration was increased from 63% to 84% (Figure 1e)
In this study we provide evidence demonstrating a direct role of APLP1 in promoting cell migration in vivo

Summary

Introduction

Amyloid precursor-like protein 1 (APLP1) is a member of the highly conserved amyloid precursor protein family that includes amyloid precursor protein (APP) and amyloid precursor-like protein 2 (APLP2) in mammals [1,2,3,4]. RNAi knock-down of APP in the developing cortex blocked the migration of neurons from the intermediate zone to the cortical www.impactjournals.com/oncotarget plate [26], suggesting a positive role of APP in neuronal migration This phenotype was not resulted from a general defect in cell motility, rather, a specific defect in the interaction between APP ectodomain and the extracellular factors, such as pancortins were detected [27]. Cultured CHO cells overexpressing APLP2 exhibited an enhanced migratory response to fibronnectin and type IV collagen through increased adhesion to these extracellular molecules [28] Together, these studies suggest that APP and APLP2 are required for cell adhesion with extracellular factors, yet a direct role of APP family proteins in promoting cell migration has not been documented

Methods

Results

Conclusion