Prömel Lab
Research
Adhesion GPCRs in development and cell polarity
Multicellular
organisms are highly
dependent on their cells to be spatially organised to form different
tissues
and organs and to develop/maintain specialised functions. For this
organisation
cells require a sense of orientation and a form of polarity. Various
types of
polarity are involved in realising these processes and it is becoming
increasingly clear that Adhesion GPCRs (aGPCRs) are vital players with
one group
of them being Latrophilins. The Latrophilin homologue LAT-1 in C. elegans is a regulator for oriented
cell division in the early embryo as well as for correct reproductive
system
function. We use the nematode C. elegans
to delineate and understand the roles of aGPCRs in development and cell
polarity. C. elegans is ideal for
these studies as it is a transparent self-fertilising organism which is
very
well characterised and offers a vast spectrum of transgenesis and
genetic
techniques.
modified from Langenhan et al., 2009 and Prömel et al., 2012
Adhesion GPCRs in metabolic processes
Adhesion GPCRs are an intriguing class of receptors. With 33 members in mammals they form the second largest group of GPCRs, but also a poorly understood one. Several aGPCRs have implications in the control of metabolic processes. We aim to uncover the physiological functions several of these receptors play in regulating fat and insulin metabolism as well as kidney function. Thereby, one main focus is on Latrophilins, GPR110, GPR111 and GPR115, which have for instance been shown to regulate insulin release or liver metabolism.
Molecular mechanisms of Adhesion GPCR activation/activity and their involvement in cellular processes
Adhesion
GPCRs are not only functionally highly diverse receptors. They also
display unique
structural features that set them apart from other GPCRs. They are
often
described as hybrids fulfilling dual roles in adhesion and signalling.
Besides
a seven transmembrane domain (7TM) their characteristic features are
their
extraordinarily long N termini encompassing various
domains
associated with cell adhesion etc. Via these extracellular
entities aGPCR mediate different functions: classical G protein
signals but also functions solely dependent on the N terminus
which are highly unusual for GPCRs.
One main focus of our work is to
understand
how aGPCRs mediate these numerous signals and the role the
extraordinarily long and complex N termini play. Using Latrophilins as
prototypic members of
the
class in the versatile model organism C.
elegans
we have identified that the receptor functions in two
different
modes in different physiological contexts. One mode relays a signal via a classical G protein-mediated
cascade
(7TM-dependent/cis), the second one is only dependent on the
receptor´s N terminus
(7TM-independent/trans). The signals behind these modes and their impact are
currently one of our main research topics. Similarly, we are
elucidating the
activation and signal transduction mechanisms of other aGPCRs.
modified from Prömel et al., 2012