Breakthroughs
- Cytoskeletal proteins have overlapping functions. Detailed
investigations of multiple gene deletions of myosins and actin binding
proteins first demonstrated this now generally accepted concept (1).
- Cytoskeletal proteins and organelles dynamically
relocalize within living cells during cytokinesis, motility, and phagocytosis
.
Actin, myosin, coronin, talin, cyclase-associated protein, and actin binding
proteins move to related regions of the cell during each of these events (2). In
addition, novel components of the cytoskeletal, including
coronin, cortellexin, and scar having been discovered in Dictyostelium.
- Conventional myosin is required for cytokinesis
. This was shown in D.
discoideum over a decade ago and has recently been duplicated in yeast (3).
Further studies of D. discoideum myosin heavy chain in vivo and as
single molecules in vitro have provided many of the known characteristics
of this molecular motor (4).
- Chemoattractants are sensed by G-protein coupled receptors
. Over a
decade ago, cloning and deletion of the cAMP receptors in D. discoideum
showed that these receptors were essential for chemotaxis (5). It is now clear
that a
family of twenty G-protein linked "chemokine" receptors mediates
chemotaxis in leukocytes.
- Gradient direction is sensed by selectively recruiting PH domains to the
membrane.
Neither surface receptors nor G-proteins are significantly
clustered at the cell’s leading edge. In addition, the actin
cytoskeleton is not required for PH domain recruitment (6). Many of these
observations have recently been duplicated in mammalian leukocytes responding
to chemokines.
- PI(3) kinase is important for controlling cell movement, cell polarity, and chemotaxis.
(7).
- Eukaryotes use two-component histidine kinases for signal transduction.
The variety of histidine kinases and response regulators in this organism has
indicated the widespread occurrence of this mode of signaling in fungi, plants
and other lower eucaryotes (8).
- A number of genes and signaling pathways found in higher eucaryotes but not
in yeast predate metazoans. These include the STAT signaling
pathway, the interplay of protein kinase A, GSK3 and in cell-type specific gene expression, and genes of the
apoptotic and Alzheimer's
disease pathways beclin and presenillin,
respectively (9).
- G-protein coupled receptors can transduce signals without G-proteins.
Receptor-mediated
G-protein independent functions include calcium influx, MAPK activation, STAT and
transcription factor activation (10). These observations fostered studies of
mammalian cells that have verified the occurrence of GPCR-mediated
G-protein-independent responses.
- Protein ubiquitination pathways are used in differentiation and pattern
formation
. Analysis of a MEKK identified the first defined in vivo
substrate of a ubiquitin protease (UBP). This work and that on a
"novel" F-box/WD40 repeat containing protein have identified new
roles of ubiquitination in controlling patterning and cell-type
determination (11).
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