10 A niversary of IIMCB

Description of Current
Research
The main research objective of the Laboratory of Cell
Biology is to study the relationship between the processes
of intracellular membrane transport and signal transduction
in response to extracellular stimuli in mammalian cells. We
aim to investigate the molecular mechanisms underlying
this mutual interdependence. In particular, the specific
projects developed in the group follow two general lines of
investigation and focus on studying:
I. the role of endosomal compartments in trafficking
and signaling of growth factors
II. the involvement of endocytic proteins in the
regulation of gene expression in the nucleus.
At a general level both topics deal with the problem of
molecular communication between intracellular organelles
in endocytic membrane transport and signal transduction.
This is a novel problem of increasing significance in the
field of cell biology, as many recent studies, including our
own, indicate that intracellular compartmentalization of
signal transduction processes may play an important role in
modulating the overall cellular response. At first endocytosis
was viewed merely as a mechanism for signal termination by
downregulation of surface receptors and their degradation.
However, more recent data strongly argues that endosomal
compartments and their resident proteins play an important
role in transmitting intracellular signals, by transporting
ligand-receptor complexes and affecting their activity
inside the cell (Miaczynska et al., 2004a). The proposal of
endosomes as signaling compartments, initially postulated
in the mid-nineties, has gained increasing experimental
support in the last few years (Sadowski et al., 2008).
Moreover, the relaying of signals from the plasma
membrane via endosomes to the nucleus requires signal
mediators to be transported between different cellular
locations. Intriguingly, a growing number of clathrin
adaptors and endosomal proteins are reported to undergo
nucleocytoplasmic shuttling. Endocytic proteins can
Fig. 1. Scheme of cargo trafficking and signaling along the endocytic pathway (author: Marta Miączyńska).
According to the classical view, ligand-receptor complexes are internalized from the plasma membrane via clathrin-coated vesicles (CCV) to early
endosomes from where they are sorted either towards recycling endosomes back to the plasma membrane or to late endosomes and lysosomes
for degradation. Our work indicates that APPL-harboring compartment represents a distinct subpopulation of early endosomes and receives cargo
from the plasma membrane via CCV and exchanges it with the canonical early endosomes. In addition to its endosomal localization, APPL proteins
can undergo nucleocytoplasmic shuttling and interact with nuclear proteins, modulating gene expression. Signal transduction, initiated by signaling
ligands binding to their receptors at the plasma membrane, can continue intracellularly from endosomal compartments during trafficking (signaling
events marked with red arrows).
Laboratory of Cell Biology 55