Triad1 regulates the expression and distribution of EHD1 contributing to the neurite outgrowth of neurons after spinal cord injury

Traumatic spinal cord injury is a common and severe complication after an accident. As we all know that neurite outgrowth of neurons is difficult after a spinal cord injury. Endosome system is associated with cargoes transportation and contributes in promoting the neuronal capability for neurite outgrowth. EH domain‐containing protein 1 (EHD1) transports proteins through the endosome system, especially in the recycling endosomes and regulating the neurite outgrowth. In mammalian cells, the involvement of the ubiquitin‐proteasome system in endosomal sorting has been well established. Two RING fingers and a DRIL (double RING finger‐linked) 1 (Triad1) plays an important role in membrane trafficking and its mutant results in the wrong accumulation of receptors in endosomes and plasma membrane. In this current study, we reasonably integrated the results of the above research and investigated the regulating function of Triad1 to EHD1 following the spinal cord injury. We characterized the upregulated expression and distribution of Triad1 and EHD1 in the neurons after SCI and declared the interaction between Triad1 with EHD1 both in vitro and in vivo. Triad1 regulated the interaction between itself and the full‐length or EH domain of EHD1, which influenced the neurite outgrowth of PC12 cells. Our data delineate a novel interaction between Triad1 and EHD1 that may contribute to the regulation of neurite outgrowth for neurons after the spinal cord injury. The entire paper nor any part of its content has been published or has been accepted else where. It is not being submitted to any other journal. We believe the paper may be of particular interest to the readers because we are the first to discover a novel Triad1‐EHD1 pathway that contributes to the regulation of neurite outgrowth of neurons after the spinal cord injury. This study will help to clarify the regulation of ubiquitin‐proteasome system and endosome system after the spinal cord injury and provide new treatment ideas for the recovery of neurological function.