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

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.

The spatial and developmental expression of mouse Vwa8 (von Willebrand domain-containing protein 8).

The Drosophila gene c12.2 was isolated in a screen examining mRNA binding proteins. Drosophila c12.2 is the mouse Vwa8 homolog. Various genome-wide associated studies have linked human Vwa8 to both neurological and oncological pathologies, which include autism, bipolar disorder, comorbid migraine, and acute myeloid leukemia, however, the function and role of the VWA8 protein remain poorly understood. To further analyze the Vwa8 gene in mouse, gene structure, protein homology modeling, and gene expression patterns were examined throughout mouse development. Our analyses indicate that the mouse Vwa8 gene produces two transcripts; the full-length Vwa8a is highly expressed relative to the truncated Vwa8b transcript across all developmental time points and tissues analyzed. Protein homology modeling indicates that VWA8a belongs to a novel protein superfamily containing both the midasin and cytoplasmic dynein 1 heavy chain 1 proteins. These data establish the development timeline and expression profile for both Vwa8a and Vwa8b, paving the way for future studies to determine the cellular role(s) of this highly conserved protein family.