K+ binding to mammalian glutamate transporters is essential for the import and release of glutamate into cells. Using MD simulations and site-directed mutagenesis, Wang et al. identify two K+ binding sites in the transporter EAAC1, one of which appears to catalyze the relocation step of the transport cycle.
Pre-assembled Ca2+ entry units and constitutively active Ca2+ entry in skeletal muscle of calsequestrin-1 knockout mice
Mice lacking calsequestrin-1 have reduced levels of releasable Ca2+ in the sarcoplasmic reticulum of their skeletal muscles. Michelucci et al. reveal that this is compensated by constitutive assembly of STIM1 and Orai1 into Ca2+ entry units, promoting both constitutive and store-operated Ca2+ entry.
Stress increases the permeability of the mitochondrial inner membrane by activating permeability transition pores (PTPs), likely composed of ATP synthase or the adenine nucleotide translocator. By measuring water flux during calcium-activated mitochondrial swelling, Neginskaya et al. estimate that if these proteins are involved in PTP, only a small fraction becomes transformed into the pore on a single mitochondrion.
The voltage-gated proton channel (HV1) resembles the voltage sensors of other channels, but its movement during channel opening remains controversial. Cherny et al. establish open and closed gating configurations of HV1 by analyzing the interactions of Zn2+ with an introduced histidine residue.
In this issue, Michelucci et al. report the existence of specific sites acting as Ca2+ entry units (CEUs) in fast skeletal muscle of mice lacking calsequestrin (CASQ1), the major Ca2+ binding protein of the SR. The CEU provides constitutive and store-operated Ca2+ entry (SOCE) and resistance to force decline resulting from SR Ca2+ depletion during repetitive muscle activity.