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Cathepsin S cannibalism of cathepsin K as a mechanism to reduce type I collagen degradation.

ABSTRACT: Cathepsins S and K are potent mammalian proteases secreted into the extracellular space and have been implicated in elastin and collagen degradation in diseases such as atherosclerosis and osteoporosis. Studies of individual cathepsins hydrolyzing elastin or collagen have provided insight into their binding and kinetics, but cooperative or synergistic activity between cathepsins K and S is less described. Using fluorogenic substrate assays, Western blotting, cathepsin zymography, and computational analyses, we uncovered cathepsin cannibalism, a novel mechanism by which cathepsins degrade each other as well as the substrate, with cathepsin S predominantly degrading cathepsin K. As a consequence of these proteolytic interactions, a reduction in total hydrolysis of elastin and type I collagen was measured compared with computationally predicted values derived from individual cathepsin assays. Furthermore, type I collagen was preserved from hydrolysis when a 10-fold ratio of cathepsin S cannibalized the highly collagenolytic cathepsin K, preventing its activity. Elastin was not preserved due to strong elastinolytic ability of both enzymes. Together, these results provide new insight into the combined proteolytic activities of cathepsins toward substrates and each other and present kinetic models to consider for more accurate predictions and descriptions of these systems.

SUBMITTER: Barry ZT

PROVIDER: S-EPMC3431690 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Cathepsin S cannibalism of cathepsin K as a mechanism to reduce type I collagen degradation.

Barry Zachary T ZT Platt Manu O MO

The Journal of biological chemistry 20120622 33

Cathepsins S and K are potent mammalian proteases secreted into the extracellular space and have been implicated in elastin and collagen degradation in diseases such as atherosclerosis and osteoporosis. Studies of individual cathepsins hydrolyzing elastin or collagen have provided insight into their binding and kinetics, but cooperative or synergistic activity between cathepsins K and S is less described. Using fluorogenic substrate assays, Western blotting, cathepsin zymography, and computation ...[more]

PMID: 22730330

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Project description:BackgroundThe consumption of conspecific young by adult individuals is a common phenomenon across various animal taxa. Possible adaptive benefits of such behaviour include the acquisition of nutrients, decreased competition for one's own offspring, and/or increased mating opportunities. Clutch cannibalism has occasionally been observed in several species of Neotropical poison frogs, but the circumstances under which this behaviour occurs has rarely been investigated experimentally. Recent experiments with the poison frog Allobates femoralis have shown that males indiscriminately transport all clutches located inside their own territory to bodies of water, but become highly cannibalistic when taking over a new territory. Females are able to indirectly discriminate between their own and foreign clutches by location and take over transport duties of their own clutches only in the absence of the father. Cannibalism by A. femoralis females has not been previously observed. We thus asked if, and under which circumstances, cannibalism of unrelated clutches by female A. femoralis would occur, by manipulating the presence of the clutch's father, the female's own reproductive state, and the female's familiarity with the environment.ResultsFemales clearly cannibalize foreign clutches. Cannibalism was most pronounced when the female had not recently produced her own clutch and the father of the foreign clutch was absent. The female's familiarity with the area had no significant influence on the likelihood of cannibalism to occur.ConclusionsOur data indicate that both previous oviposition and the father's presence reduce cannibalistic behaviour in A. femoralis females. Cannibalistic females may gain nutritional benefits or enhanced inclusive fitness by preying on other females' offspring. The finding that the father's presence at the clutch site/territory was sufficient to reduce cannibalism by females suggests a prominent role of male territoriality for the evolution of male parental care.

Dataset Information

Cathepsin S cannibalism of cathepsin K as a mechanism to reduce type I collagen degradation.

Publications

Cathepsin S cannibalism of cathepsin K as a mechanism to reduce type I collagen degradation.

Similar Datasets

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