Rab27a-Dependent Paracrine Communication Controls Dendritic Spine Formation and Sensory Responses in the Barrel Cortex.

Longbo Zhang,Lawrence S Hsieh,Xiaobing Zhang,Angélique Bordey,Tiffany V Lin

doi:10.3390/cells10030622

Longbo Zhang, Lawrence S Hsieh + Show 3 more

Open Access

https://doi.org/10.3390/cells10030622

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Journal: Cells	Publication Date: Mar 11, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: Yale University, Florida State University

Abstract

Rab27a is an evolutionarily conserved small GTPase that regulates vesicle trafficking, and copy number variants of RAB27a are associated with increased risk of autism. However, the function of Rab27a on brain development is unknown. Here, we identified a form of paracrine communication that regulates spine development between distinct populations of developing cortical neurons. In the developing somatosensory cortex of mice, we show that decreasing Rab27a levels in late-born pyramidal neurons destined for layer (L) 2/3 had no cell-autonomous effect on their synaptic integration but increased excitatory synaptic transmission onto L4 neurons that receive somatosensory information. This effect resulted in an increased number of L4 neurons activated by whisker stimulation in juvenile mice. In addition, we found that Rab27a, the level of which decreases as neurons mature, regulates the release of small extracellular vesicles (sEVs) in developing neurons in vitro and decreasing Rab27a levels led to the accumulation of CD63-positive vesicular compartments in L2/3 neurons in vivo. Together, our study reveals that Rab27a-mediated paracrine communication regulates the development of synaptic connectivity, ultimately tuning responses to sensory stimulation, possibly via controlling the release of sEVs.

Highlights

Whole-cell patch-clamp recordings of electroporated neurons revealed that Rab27a shRNA did not alter their resting membrane potential, input resistance, and intrinsic excitability (Figure 1G,H)
Using patch-clamp recordings of neighboring non-electroporated neurons in the same cultures (Figure 1K), we found that Rab27a shRNA did not affect paired pulse ratio, a read-out of release probability (Figure 1L,M)
Considering Rab27a’s role in vesicular trafficking, including the fusion of multivesicular body (MVB) resulting in the release of intraluminal vesicles (ILs) into the extracellular space that are called small extracellular vesicles (sEVs) or exosomes [15,16,17,18,19,20,21], we investigated whether synaptic and biophysical properties of non-electroporated neurons nearby Rab27a shRNA-expressing neurons were altered