Regulation and Function of the Caspase-1 in an Inflammatory Microenvironment.

The inflammasome is a complex of proteins that has a critical role in mounting an inflammatory response in reply to a harmful stimulus that compromises the homeostatic state of the tissue. The NLRP3 inflammasome, which is found in a wound-like environment, is comprised of three components: the NLRP3, the adaptor protein ASC and caspase-1. Interestingly, although ASC levels do not fluctuate, caspase-1 levels are elevated in both physiological and pathological conditions.

Dynamic expression of epidermal caspase 8 simulates a wound healing response.

Tissue homeostasis and regeneration are regulated by an intricate balance of seemingly competing processes-proliferation versus differentiation, and cell death versus survival. Here we demonstrate that the loss of epidermal caspase 8, an important mediator of apoptosis, recapitulates several phases of a wound healing response in the mouse. The epidermal hyperplasia in the caspase 8 null skin is the culmination of signals exchanged between epidermal keratinocytes, dermal fibroblasts and leukocytic cells.

Regulation of Rap1 activity by RapGAP1 controls cell adhesion at the front of chemotaxing cells.

Spatial and temporal regulation of Rap1 is required for proper myosin assembly and cell adhesion during cell migration in Dictyostelium discoideum. Here, we identify a Rap1 guanosine triphosphatase-activating protein (GAP; RapGAP1) that helps mediate cell adhesion by negatively regulating Rap1 at the leading edge. Defects in spatial regulation of the cell attachment at the leading edge in rapGAP1- (null) cells or cells overexpressing RapGAP1 (RapGAP1(OE)) lead to defective chemotaxis.

Rap1 controls cell adhesion and cell motility through the regulation of myosin II.

We have investigated the role of Rap1 in controlling chemotaxis and cell adhesion in Dictyostelium discoideum. Rap1 is activated rapidly in response to chemoattractant stimulation, and activated Rap1 is preferentially found at the leading edge of chemotaxing cells. Cells expressing constitutively active Rap1 are highly adhesive and exhibit strong chemotaxis defects, which are partially caused by an inability to spatially and temporally regulate myosin assembly and disassembly.