Featured Papers in 2018

TrkB Signals as a Monomer and not a Dimer from the Plasma Membrane

Zahavi, E.E. et al. (2018) Sci. Signal. 11, eaao4006.

TrkB-BDNF signaling is responsible and involved in cell proliferation, differentiation, cell survival, and long-term potentiation.

In a recent game changing paper, Zahavi et al. elegantly and remarkably refute the current model of tyrosine kinase receptor activation. TrkB, the receptor for BDNF, does not undergo dimerization at the cell membrane following BDNF activation.

The authors show that TrkB signals as a monomer from the plasma membrane upon activation through a series of complex experiments involving recombinant/chimeric proteins, immunostaining and microscopy. Alomone Labs human BDNF-Biotin (#B-250-B) plays a pivotal role in this explicitly controversial, formidable, and exciting paper. Using biotinylated BDNF, the authors show that monomeric TrkB receptors bind BDNF (Figure 1) by a coordinated lateral movement of both proteins.

Following stimulation by BDNF, the receptor-ligand complex is internalized in endosomes where the signal is propagated spatially and temporally. Biotinylated BDNF is shown to internalize with TrkB into endosomes. However, in endosomes, TrkB appears as a dimer and the authors propose that a ligand-dependent dimerization occurs within signaling endosomes. This study leads to open questions like what factors are involved in TrkB dimerization in the endosome.

Figure 1. TrkB binds to BDNF at the plasma membrane.Live TIRF imaging of TrkB-ACP-488 and labeled BDNF co-movement in HEK293T (HEK). Cells treated with streptavidin-647-labeled human BDNF-Biotin (#B-250-B) for 5 minutes and imaged at 8 fps. Arrowhead marks co-localized TrkB-BDNF particle. Scale bar = 2 µm. Right: color trace shows movement trajectory of TrkB-ACP-488 and BDNF-647 particles over time (blue- start, red- end of trajectory) Scale bar = 1 µm.Unpublished data from Zahavi, E.E. et al. (2018) Sci. Signal. 11, eaao4006. Figure generously provided by Dr. Eran Perlson, Dept. of Physiology and Pharmacology, Tel-Aviv University, Tel-Aviv, Israel.

Presynaptic KV3.4 Channel Regulates Nociceptive Glutamatergic Signaling in Spinal Dorsal Horn

Muqeem, T. et al. (2018) J. Neurosci. 38, 3729.

Lipopolysaccharides Activate BK/KCa1.1 Channels in Bladder Umbrella Cells

Lu, M. et al. (2018) Am. J. Physiol. 314, C643.

Blocking TRPV4 as a Means of Maintaining BBB Integrity

Zhao, H. et al. (2018) Front. Mol. Neurosci. 11, 97.

Accumulation of CaV3.2 in Uninjured Sural Nerve – A Role in Peripheral Sensitization & Neuropathic Pain

Chen, W. et al. (2018) Front. Mol. Neurosci. 11, 24.

Piezo1 Mediates Pressure-Induced Pancreatitis

Romac, J.M. et al. (2018) Nat. Commun. 9, 1715.