TRPM7 is critical for short-term synaptic depression by regulating synaptic vesicle endocytosis.

Zhong-Jiao Jiang,Wenping Li,Ying S Hu,Simon Alford,Andrea Mcginley,Badeia Saed,Kelly Varga,Li-Hua Yao,Liang-Wei Gong,Yan Rao,Brian S Grewe

doi:10.7554/elife.66709

Abstract

Transient receptor potential melastatin 7 (TRPM7) contributes to a variety of physiological and pathological processes in many tissues and cells. With a widespread distribution in the nervous system, TRPM7 is involved in animal behaviors and neuronal death induced by ischemia. However, the physiological role of TRPM7 in central nervous system (CNS) neuron remains unclear. Here, we identify endocytic defects in neuroendocrine cells and neurons from TRPM7 knockout (KO) mice, indicating a role of TRPM7 in synaptic vesicle endocytosis. Our experiments further pinpoint the importance of TRPM7 as an ion channel in synaptic vesicle endocytosis. Ca2+ imaging detects a defect in presynaptic Ca2+ dynamics in TRPM7 KO neuron, suggesting an importance of Ca2+ influx via TRPM7 in synaptic vesicle endocytosis. Moreover, the short-term depression is enhanced in both excitatory and inhibitory synaptic transmissions from TRPM7 KO mice. Taken together, our data suggests that Ca2+ influx via TRPM7 may be critical for short-term plasticity of synaptic strength by regulating synaptic vesicle endocytosis in neurons.

Highlights

Transient receptor potential melastatin 7 (TRPM7), an ubiquitously expressed member of transient receptor potential (TRP) superfamily (Nadler et al, 2001; Ramsey et al, 2006; Venkatachalam and Montell, 2007), is a cation channel fused with an unique alpha-kinase domain on its C terminus (Nadler et al, 2001)
Since localizations of TRPM7 to synaptic vesicles has been implied from previous studies (Brauchi et al, 2008; Krapivinsky et al, 2006), to examine any potential TRPM7 openings during endocytosis, we performed double patch recordings, in which the cell-attached patch pipette was utilized to monitor both endocytic events and the ionic current across the patch membrane
TRPM7 KO neurons (Figure 3-figure supplement 6, Figure 3-figure supplement 6-source 210 data). These results suggest that TRPM7 may not be critical for exocytosis of synaptic vesicles in inhibitory synapses with electrically neutral GABA or excitatory synapses with negatively charged glutamate as the predominant neurotransmitters, it is aware that a previous study implies that TRPM7 may have a post-fusion role by supplying counterions during release of positively charged acetylcholine in peripheral nervous system (PNS) sympathetic neurons (Krapivinsky et al, 2006; Montell, 2006)

Summary

Introduction

Transient receptor potential melastatin 7 (TRPM7), an ubiquitously expressed member of transient receptor potential (TRP) superfamily (Nadler et al, 2001; Ramsey et al, 2006; Venkatachalam and Montell, 2007), is a cation channel fused with an unique alpha-kinase domain on its C terminus (Nadler et al, 2001). In PNS sympathetic neurons (Krapivinsky et al., 2006), it is reported that TRPM7 may regulate release of positively charged acetylcholine during vesicle fusion through a proposed ion compensation mechanism (Krapivinsky et al, 2006; Montell, 2006). It remains largely unknown what the physiological function of presynaptic TRPM7 is in CNS neurons. By using a combination of biophysical, molecular biology, electrophysiological and live-cell imaging methods, the present study has identified that Ca2+ influx via TRPM7 may be critical for short-term changes of synaptic strength by regulating synaptic vesicle endocytosis in CNS neurons

Results

Discussion

Materials and Methods