Anti-BMP1 (aa 972-986) polyclonal antibody

Background: Extracellular matrix protein PCPE2 is linked to alterations in HDL size and concentration. Results: PCPE2 protects against diet-induced atherosclerosis by promoting HDL catabolism, reverse cholesterol transport, and SR-BI-mediated uptake of HDL-cholesteryl ester. Conclusion: PCPE2 mediates HDL function by reducing lipid and immune cell accumulation in the artery. Significance: These findings establish a role for the extracellular matrix glycoprotein PCPE2 in SR-BI-mediated HDL function and the prevention of atherosclerosis. Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor-deficient mice to obtain LDLr-/-, PCPE2(-/-) mice, which had elevated HDL levels compared with LDLr-/- mice with similar LDL concentrations. We found that LDLr-/-, PCPE2(-/-) mice had significantly more neutral lipid and CD68+ infiltration in the aortic root than LDLr-/- mice. Surprisingly, in light of their elevated HDL levels, the extent of aortic lipid deposition in LDLr-/-, PCPE2(-/-) mice was similar to that reported for LDLr-/-, apoA-I-/- mice, which lack any apoA-I/HDL. Furthermore, LDLr-/-, PCPE2(-/-) mice had reduced HDL apoA-I fractional clearance and macrophage to fecal reverse cholesterol transport rates compared with LDLr-/- mice, despite a 2-fold increase in liver SR-BI expression. PCPE2 was shown to enhance SR-BI function by increasing the rate of HDL-associated cholesteryl ester uptake, possibly by optimizing SR-BI localization and/or conformation. We conclude that PCPE2 is atheroprotective and an important component of the reverse cholesterol transport HDL system.

Conidial germination of the grey mould fungus Botrytis cinerea was found to be induced by different chemical and physical signals, namely the amount and quality of nutrients as well as the hydrophobicity and rigidity of the surface. A B. cinerea Delta bcg3 mutant disrupted in the G alpha 3 subunit of the heterotrimeric G protein was specifically defective in germination induced by carbon sources. A similar germination defect of an adenylate cyclase mutant, and the complementing effect of cAMP addition to conidia of these mutants confirmed the involvement of cAMP. In contrast, a Delta bmp1 MAP kinase mutant was delayed in carbon source-induced germination, but completely unable to germinate on hydrophobic surfaces. Based on these data, it is proposed that the germination response of B. cinerea conidia is controlled by three signalling pathways: Germination induction by rich media is weakly dependent on BMP1; induction by carbon sources requires BCG3, cAMP and BMP1; and induction by contact to hydrophobic surfaces is absolutely dependent on BMP1. Other defects of the Delta bcg3 mutant, such as low conidiation, excessive formation of sclerotia and delayed host infection, were also restored by cAMP. Microscopical studies of germling growth and differentiation on host cuticles revealed that the delayed infection of the Delta bcg3 mutant was due to a surface sensing defect leading to a reduced penetration. Thus, in addition to their role in germination, G alpha 3, cAMP as well as BMP1 are required also for proper host surface recognition and penetration ability of germinated conidia.