Receptor Oligomerization as a Process Modulating Cellular Semiotics

The majority of G protein-coupled receptors (GPCRs) self-assemble in
the form dimeric/oligomeric complexes along the plasma membrane. Due to the
molecular interactions they participate, GPCRs can potentially provide the
framework for discriminating a wide variety of intercellular signals, as based
on some kind of combinatorial receptor codes. GPCRs can in fact transduce
signals from the external milieu by modifying the activity of such intracellular
proteins as adenylyl cyclases, phospholipases and ion channels via interactions
with specific G-proteins. However, in spite of the number of cell functions they
can actually control, both GPCRs and their associated signal transduction
pathways are extremely well conserved, for only a few alleles with null or
minor functional alterations have so far been found. This would seem to suggest
that, beside a mechanism for DNA repairing, there must be another level of
quality control that may help maintaining GPCRs rather stable throughout
evolution. We propose here receptor oligomerization to be a basic molecular
mechanism controlling GPCRs redundancy in many different cell types, and the
plasma membrane as the first hierarchical cell structure at which selective
categorical sensing may occur. Categorical sensing can be seen as the cellular
capacity for identifying and ordering complex patterns of mixed signals out of a
contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous
signals. In this context, redundancy and degeneracy may appear as the required
feature to integrate the cell system into functional units of progressively higher
hierarchical levels.