Cleaning up? Not without helpers

October 19, 2017

Calcium-ATPases convey calcium ions (Ca2+) from the cytoplasm to the extracellular space via active transport (using ATP as an energy source), and thus fundamentally contribute to the control of a wide variety of Ca2+-dependent processes in virtually any type of cell in humans and animals. Scientists in the group of Dr. Uwe Schulte and Prof. Dr. Bernd Fakler at the Institute of Physiology at the University of Freiburg have successfully unraveled the molecular appearance of this well-known 'ion pump': Different from classical textbook knowledge, Ca2+-pumps of the plasma membrane (PMCAs) are identified as protein complexes that are assembled from two ATP-hydrolyzing transporter proteins and two as yet unknown subunits, Neuroplastin and Basigin. These two novel protein subunits are essential for stability and trafficking of the PMCA complexes to the plasma membrane and control the PMCA-mediated Ca2+-transport. The researchers have presented their work in the current issue of the scientific journal Neuron.

A variety of cellular processes such as release of transmitters and hormones, regulation of enzymatic activities and excitability, contraction or cell motility are controlled by intracellular Ca2+. These processes are switched on by Ca2+-influx, mostly through Ca2+-permeable ion channels, and they are switched off by Ca2+-ATPases in the plasma membrane, the PMCAs. The Fakler group has now shown that this switch-off by PMCAs may only take a few ten milliseconds, in contrast to the seconds-lasting periods assumed previously. As the mechanism behind this unexpectedly high efficiency in Ca2+-transport activity, the researchers identified co-assembly of the ATPase subunits with the auxiliary proteins Neuroplastin and Basigin which promote effective integration of the PMCA complexes into the plasma membrane. Deletion of both Neuroplastin and Basigin in CNS neurons leads to severe disturbance of neuron signal transduction and ultimately to cell death.

Even before their identification as auxiliary subunits of PMCA complexes, Neuroplastin and Basigin have not been 'unknowns'. In fact, investigations by several groups predominantly on knock-out animals and tissues demonstrated fundamental involvement of both proteins in quite a variety of different cellular processes ranging from formation, operation and plasticity of synapses in central neurons, to spermatogenesis and fertilization, or infection of erythrocytes by plasmodium, the pathogen of malaria. So far, however, the molecular mechanisms underlying these processes have remained unresolved. Based on the newly established results by the Freiburg scientists, it appears reasonable to assume that all the aforementioned processes share a common mechanism - the PMCA-mediated control of intracellular Ca2+-signaling.
-end-
Bernd Fakler is the director of Department II of the Institute of Physiology and area coordinator of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies at the University of Freiburg.

Original publication:

Schmidt N, Kollewe A, Constantin CE, Henrich S, Ritzau-Jost A, Bildl W, Saalbach A, Hallermann S, Kulik A, Fakler B, Schulte U. Neuroplastin and Basigin are essential auxiliary subunits of plasma membrane Ca2+-ATPases and key regulators of Ca2+ clearance. Neuron (online on Oct 19th), 2017.

https://doi.org/10.1016/j.neuron.2017.09.038

University of Freiburg

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.