Presynaptic protein synaptotagmin1 regulates the activity‐induced remodeling of synaptic structures in cultured hippocampal neurons

Abstract

Activity-dependent reorganizations of central neuronal synapses are thought to play important roles in learning and memory. Although the precise mechanisms of how neuronal activities modify synaptic connections in neurons remain to be clarified, the activity-induced neuronal presynaptic proteins such as synaptotagmin1 may contribute to the onset of synaptic remodeling. To understand better the physiological roles of synaptotagmin1, we first examined the prolonged effects of neuronal stimulation capable of inducing synaptotagmin1 on the distribution of a postsynaptic proteins (PSD) protein Homer1c by immunostaining. Previously we found that glutamate stimulation induced other postsynaptic proteins, such as postsynaptic density-95 (PSD95), a biphasic change with an initially diffuse distribution after 30 min to 1 hr, followed by reassembly to more than the original level after 4-8 hr, suggesting that glutamate stimulation induces a global biphasic alteration in synaptic structures. To dissect further the functions of synaptotagmin1 in the activity-induced synaptic remodeling, short hairpin RNA (shRNA) vectors that specifically block the expression of endogenous synaptotagmin1 were constructed. When the shRNA of synaptotagmin1 was introduced to the neurons, the activity-induced changes were almost completely suppressed. We found that synaptotagmin1 contributes to the postsynaptic remodeling in a retrograde manner. Our data indicate that synaptotagmin1 regulates the activity-induced biphasic changes of post- and presynaptic sites.

Expression and secretion of synaptic proteins during stem cell differentiation to cortical neurons

“…SYT-1 is a pre-synaptic calcium-binding synaptic vesicle protein known to be expressed in cerebral cortex, hippocampus and cerebellum ( Chen et al, 2013 ; Sudhof and Rizo, 2011 ). It is suggested that SYT-1 has a role in exocytosis and endocytosis, synapse function, behavioral cognition, neuronal polarity, axon differentiation, neuro-development and activity-induced remodeling of synaptic structures ( Baker et al, 2015 ; Inoue et al, 2013 , 2015 ; Sudhof and Rizo, 2011 ).…”

Lactate promotes neuronal differentiation of SH-SY5Y cells by lactate-responsive gene sets through NDRG3-dependent and -independent manners

“…NPY ( 32 , 33 , 34 , 35 ) and SCG2 ( 29 ), important differentiation markers of neural cells, were ranked in the top 20 of upregulated genes by lactate. Neuronal differentiation-related genes including AGRN ( 53 ), SOX9 ( 54 , 55 ), TLE ( 56 , 57 ), MEST ( 58 ), CLU ( 59 ), NCAM1 ( 60 ), NGFR ( 61 ), NRCAM ( 62 , 63 ), SYT1 ( 64 ), SYT4 ( 65 ), and SYT11 ( 66 ) were also upregulated in both SH-SY5Y and Neuro2A under lactate treatment. Other crucial neural differentiation regulators such as RUNX1T1 ( 67 , 68 ), SPARCL1 ( 69 ), NPAS3 ( 70 ), CEND1 ( 71 ), SYT9 ( 72 ), and SYP ( 73 ) were upregulated only in SH-SY5Y cells.…”