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

Abstract

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.

Ubiquitin ligase Triad1 promotes neurite outgrowth by inhibiting MDM2-mediated ubiquitination of the neuroprotective factor pleiotrophin

“…Another study identified that knockdown of Triad1 reduces apoptosis of spinal cord neurons (21). Triad1 contributes to the neurite outgrowth of neurons after SCI (4,22), and plays an important role in the proliferation and differentiation of neural stem cells following traumatic brain injury (8). Of note, astrocytes secrete neurotrophic factors to promote and stabilize the function of neurons in nervous system (6).…”

“…After SCI, regenerated neurons are almost nonexistent so that the restoration of nerve function only depends on the remaining neurons. However, neurons possess limited abilities to grow neurite during the repair, and the utilization of growth factors and neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) is insufficient ( 4 , 5 , 6 ). These two aspects, therefore, need to be improved for the functional recovery of patients with SCI.…”

Triad1 Promotes the Inflammatory Response and Neuronal Apoptosis to Aggravate Acute Spinal Cord Injury in Rats

“…Additionally, Triad1 is involved in bone marrow colony formation and cell cycle regulation by interacting with its binding proteins [ 15 , 18 ]. Triad1 can interact with EH domain-containing protein 1 (EHD1) to further regulate the neurite outgrowth of neurons after SCI [ 19 ]. Moreover, it has also been indicated that Triad1 can promote neuronal apoptosis after SCI by regulating the p53-Caspase3 pathway [ 12 ].…”

The decreased expression of miR-429 in plasma exosomes after spinal cord injury inhibits neuronal apoptosis by mediating the PTEN/PI3K/Akt pathway

“…Each sample was placed in a sampling vessel, and centrifuged at 1,200 g at 4 ℃ for 10 min. The supernatant (plasma) was carefully transferred into Eppendorf tubes and frozen at -80 ℃ for subsequent experiments (20). A protocol was prepared before the study without registration.…”