【Research Trends】Ma Cong's research group reveals the molecular mechanism of Rabphilin 3A regulating cytosis secretion in neuroendocrine cells

On September 29, 2022, Professor Ma Cong's research group of the School of Life Sciences and Technology of Huazhong University of Science and Technology published a research paper
entitled "Rabphilin 3A binds the N-peptide of SNAP-25 to promote SNARE complex assembly in exocytosis" in eLife, an authoritative journal in the field of biology.

Figure 1.
Exchange of information between neurons and neuroendocrine cells and target cells

Neurons and neuroendocrine cells act on target cells by secreting important signaling molecules such as neurotransmitters and hormones to complete cell-to-cell communication (Figure 1
).
The SNARE complex is the core power engine
that drives the process.
The three SNARE proteins syntaxin-1, synaptobrevin-2 and SNAP-25 mediate follicles and plasma membrane fusion by forming a SNARE complex to complete the rapid secretion
of signaling molecules such as neurotransmitters or hormones.
To complete efficient secretion events, SNARE proteins require high activation to complete efficient SNARE complex assembly
.
In recent years, Ma Cong's research group has systematically elucidated the functional mechanism of Munc13 and Munc18 as molecular templates for co-activating syntaxin-1 and synaptobrevin-2 (The EMBO Journal, 2017; Nature Communications, 2019; The EMBO Journal, 2020）
。 However, at present, domestic and foreign research still lacks understanding
of the activation mechanism of SNAP-25.

Using biochemical, biophysical, and TIRF imaging methods, the study found that Rabphilin 3A accelerates the SNARE complex assembly efficiency and rate
by inducing the SNARE motif of the SNAP-25 protein to form a α helix by binding to the N-terminal small peptide of SNAP-25.
The promoting effect of Rabphilin 3A was confirmed
within neuroendocrine cells.
Disrupting the interaction between Rabphilin 3A and SNAP-25 will significantly affect the secretion level
of dense core vesicles (DCVs) within PC12 cells.
The study proposes a new model of Rabphilin 3A to accelerate SNARE complex assembly by activating SNAP-25 (Figure 2), providing new hypotheses and models
for the study of the mechanism of vesicle exocytosis secretion in neurons and neuroendocrine cells.

Figure 2.
Rabphilin 3A regulates SNARE complex assembly pattern diagram (syntaxin-1: Syx1; synaptobrevin-2: Syb2; SNAP-25: SN25; Rabphilin 3A: Rph3A）

Professor Ma Cong, School of Life Science and Technology, Huazhong University of Science and Technology, is the corresponding author of the paper, Li Tianzhi, a doctoral student in the School of Life Science and Technology of Huazhong University of Science and Technology, is the first author of the paper, and Cheng Qiqi, a master's student, and Wang Shen, a postdoctoral student, jointly participated in the research of
the paper.
The research has been funded by major national science and technology projects and the National Natural Science Foundation of China
.

Paper Link: https://elifesciences.
org/articles/79926

Pubmed：https://pubmed.
ncbi.
nlm.
nih.
gov/36173100/