Fruh, S. | Search bioRxiv

bioRxiv2023

Glutamate Transporters are Involved in Direct Inhibitory Synaptic Transmission in the Vertebrate Retina

In the central nervous system of vertebrates, glutamate serves as the primary excitatory neurotransmitter. However, in the retina, glutamate released from photoreceptors causes hyperpolarization in postsynaptic ON-bipolar cells through a glutamate-gated chloride current, which seems paradoxical. Our research reveals that this current is modulated by two excitatory glutamate transporters, EAAT5b and EAAT7. These transporters are located at the dendritic tips of ON-bipolar cells and interact with all four types of cone photoreceptors. The absence of these transporters leads to a decrease in ON-bipolar cell responses, with eaat5b mutants being more severely affected than eaat5b/eaat7 double mutants, which also exhibit altered response kinetics. Biophysical investigations establish that EAAT7 is an active glutamate transporter with a predominant anion conductance. Our study is the first to demonstrate the direct involvement of postsynaptic glutamate transporters in inhibitory direct synaptic transmission at a central nervous system synapse.

neuroscience↗

bioRxiv2020

Platelets exploit fibrillar adhesions to assemble fibronectin matrix revealing new force-regulated thrombus remodeling mechanisms

Upon vascular injury, platelets are crucial for thrombus formation and contraction, but do they directly initiate early tissue repair processes? Using 3D super-resolution microscopy, micropost traction force microscopy, and specific integrin or myosin IIa inhibitors, we discovered here that platelets form fibrillar adhesions. They assemble fibronectin nanofibrils using IIb{beta}3 (CD41/CD61, GPIIb-IIIa) rather than 5{beta}1 integrins, in contrast to fibroblasts. Highly contractile platelets in contact with thrombus proteins (fibronectin, fibrin) pull fibronectin fibrils along their apical membrane, whereas platelets on basement membrane proteins (collagen IV, laminin) are less contractile generating less stretched planar meshworks beneath themselves. As probed by vinculin-decorated talin unfolding, platelets on fibronectin generate similar traction forces in apical fibrillar adhesions as fibroblasts do. These are novel mechanobiology mechanisms by which platelets spearhead the fibrillogenesis of the first de novo ECM, including its 2D versus 3D network architectures depending on their ECM environment, and thereby pave the way for cell infiltration.

cell biology↗