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The calpains: modular designs and functional diversity.

ABSTRACT: The calpain family is named for the calcium dependence of the papain-like, thiol protease activity of the well-studied ubiquitous vertebrate enzymes calpain-1 (mu-calpain) and calpain-2 (m-calpain). Proteins showing sequence relatedness to the catalytic core domains of these enzymes are included in this ancient and diverse eukaryotic protein family. Calpains are examples of highly modular organization, with several varieties of amino-terminal or carboxy-terminal modules flanking a conserved core. Acquisition of the penta-EF-hand module involved in calcium binding (and the formation of heterodimers for some calpains) seems to be a relatively late event in calpain evolution. Several alternative mechanisms for binding calcium and associating with membranes/phospholipids are found throughout the family. The gene family is expanded in mammals, trypanosomes and ciliates, with up to 26 members in Tetrahymena, for example; in striking contrast to this, only a single calpain gene is present in many other protozoa and in plants. The many isoforms of calpain and their multiple splice variants complicate the discussion and analysis of the family, and challenge researchers to ascertain the relationships between calpain gene sequences, protein isoforms and their distinct or overlapping functions. In mammals and plants it is clear that a calpain plays an essential role in development. There is increasing evidence that ubiquitous calpains participate in a variety of signal transduction pathways and function in important cellular processes of life and death. In contrast to relatively promiscuous degradative proteases, calpains cleave only a restricted set of protein substrates and use complex substrate-recognition mechanisms, involving primary and secondary structural features of target proteins. The detailed physiological significance of both proteolytically active calpains and those lacking key catalytic residues requires further study.

SUBMITTER: Croall DE

PROVIDER: S-EPMC2394746 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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The calpains: modular designs and functional diversity.

Croall Dorothy E DE Ersfeld Klaus K

Genome biology 20070101 6

The calpain family is named for the calcium dependence of the papain-like, thiol protease activity of the well-studied ubiquitous vertebrate enzymes calpain-1 (mu-calpain) and calpain-2 (m-calpain). Proteins showing sequence relatedness to the catalytic core domains of these enzymes are included in this ancient and diverse eukaryotic protein family. Calpains are examples of highly modular organization, with several varieties of amino-terminal or carboxy-terminal modules flanking a conserved core ...[more]

PMID: 17608959

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Project description:BackgroundExchangeable neck stems, defined as those with a dual taper (that is, a modular junction between the femoral head and the femoral neck and an additional junction between the neck and the stem body), were introduced in THA to improve restoration of joint biomechanics (restoring anteversion, offset, and limb length) and reduce the risk of dislocation. However exchangeable necks have been reported to result in adverse effects such as stem fractures and acute local tissue reaction. Whether they result in a net improvement to or impairment of reconstructive survivorship remains controversial.Questions/purposes(1) To compare the prosthetic survivorship and all-cause revision risk of exchangeable femoral neck THAs versus fixed neck THAs, taking known prosthetic revision risk factors into account; and (2) to compare the cause-specific revision risk of exchangeable femoral neck THAs versus fixed neck THAs, adjusting for known prosthetic risk factors.MethodsUsing French national health-insurance databases, we identified all French patients older than 40 years who underwent primary THA from 2009 through 2012. To ensure accuracy of the data, we considered only beneficiaries of the general insurance scheme (approximately 77% of the population). Characteristics of the prosthesis and the patients receiving an exchangeable femoral neck THA were compared with those receiving a fixed femoral neck THA (defined as femoral stem with only the head being exchangeable). Revision was the event of interest. Followup started on the date the THA was performed, until the patient experienced revision, died, was lost to followup, or until the followup period ended (December 31, 2014), whichever came first. Competing risk THA survivorship was calculated and compared (purpose 1), as were cause-specific Cox regression models (purpose 2). The study cohort included 324,108 individuals with a mean age of 77 years. A total of 24% underwent THA for acute trauma, and 3% of the group received an exchangeable neck THA. During the median 45-month followup (mean, 42 months; minimum, 1 day; maximum, 6 years), 11,968 individuals underwent prosthetic revision.ResultsThe cumulative revision incidence was 6.5% (95% CI, 5.8%-7.3%) for exchangeable neck THAs versus 4.7% (95% CI, 4.6%-4.8%) for fixed neck THAs (p < 0.001). After controlling for potential confounding variables including age, sex, comorbidities, indication for THA, cementation, bearing surface, and the characteristics of the center where the implantation was performed, we found that the exchangeable femoral neck THA was associated with an increased hazard ratio (HR) of revision of 1.26 (95% CI, 1.14-1.38; p < 0.001) compared with the fixed neck THA. When dealing with cause-specific revision, exchangeable neck THAs had a higher incidence of revision for implant failure or periprosthetic fracture, and for mechanical complications; adjusted HRs were, respectively, 1.68 (95% CI, 1.24-2.27; p < 0.001) and 1.27 (95% CI, 1.13-1.43; p < 0.001), for exchangeable neck THAs compared with fixed ones.ConclusionsExchangeable neck THAs had poorer survivorship independent of other prosthetic revision risk factors. Accordingly, expected anatomic and functional benefits should be carefully assessed before choosing this design.Level of evidenceLevel III, therapeutic study.

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The calpains: modular designs and functional diversity.

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The calpains: modular designs and functional diversity.

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