An apical Phe-His pair defines the Orai1-coupling site and its occlusion within STIM1.

Ca signal-generation through inter-membrane junctional coupling between endoplasmic reticulum (ER) STIM proteins and plasma membrane (PM) Orai channels, remains a vital but undefined mechanism. We identify two unusual overlapping Phe-His aromatic pairs within the STIM1 apical helix, one of which (F394-H398) mediates important control over Orai1-STIM1 coupling. In resting STIM1, this locus is deeply clamped within the folded STIM1-CC1 helices, likely near to the ER surface.

Cold sensory transduction through the STIM-Orai signaling pathway.

The STIM-Orai signaling pathway mediates Ca signals vital for controlling transcription and cell growth. The Ca sensing STIM proteins are activated by depletion of Ca stored in the ER, and translocate into ER-PM junctions to gate PM Orai channels. STIM1 activation also results from heating STIM1 proteins, and new evidence reveals the STIM1-mediated gating of Orai1 channels is activated by noxious cooling of cells.

Unidentified Branches of the Posterior Femoral Cutaneous Nerve and Persistent Neuropathy.

The posterior femoral cutaneous nerve (PFCN) is an extensive nerve with numerous collateral branches which provide cutaneous innervation to 2/3 of the posterior thigh, the infragluteal fold, as well as the lateral anal region, scrotum, and labia majora through its inferior cluneal and pudendal nerve branches. It has been noted in multiple studies that patients can experience persistent PFCN neuropathy after surgery for decompression of known collateral branches. In this study, we used 17 formaldehyde (7 male and 10 female) perfused cadavers obtained from Hershey Medical Center's donor program to study the branching patterns of the PFCN.

Orai channel C-terminal peptides are key modulators of STIM-Orai coupling and calcium signal generation.

Junctional coupling between endoplasmic reticulum (ER) Ca-sensor STIM proteins and plasma membrane (PM) Orai channels mediates Ca signals in most cells. We reveal that PM-tethered, fluorescently tagged C-terminal M4x (fourth transmembrane helix contains a cytoplasmic C-terminal extension) peptides from Orai channels undergo a Leu-specific signature of direct interaction with the STIM1 Orai-activating region (SOAR), exactly mimicking STIM1 binding to gate Orai channels. The 20-amino-acid Orai3-M4x peptide associates avidly with STIM1 within ER-PM junctions, functions to competitively block native Ca signals, and mediates a key modification of STIM-Orai coupling induced by 2-aminoethoxydiphenyl borate.

Internal Neurolysis of the Common Peroneal Nerve With Lower Extremity Flexion Increases Likelihood for Direct End-End Nerve Repairs.

Introduction An understanding of common peroneal neuropathy is essential to improving current surgical techniques and overcoming limitations of permanent common peroneal nerve (CPN) damage, which negatively impacts quality of life. This study focuses on quantifying additional nerve length after CPN internal neurolysis with varying degrees of lower extremity flexion, in order to improve end-end nerve repairs in the setting of injury with a significant gap. Materials and methods Full and partial neurolysis dissections were performed on salt- and formaldehyde-perfused cadavers.