[
Cell Death Differ,
2018]
The apoptosome is a platform that activates apical procaspases in response to intrinsic cell death signals. Biochemical and structural studies in the past two decades have extended our understanding of apoptosome composition and structure, while illuminating the requirements for initiator procaspase activation. A number of studies have now provided high-resolution structures for apoptosomes from C. elegans (CED-4), D. melanogaster (Dark), and H. sapiens (Apaf-1), which define critical protein interfaces, including intra and interdomain interactions. This work also reveals interactions of apoptosomes with their respective initiator caspases, CED-3, Dronc and procaspase-9. Structures of the human apoptosome have defined the requirements for cytochrome c binding, which triggers the conversion of inactive Apaf-1 molecules to an extended, assembly competent state. While recent data have provided a detailed understanding of apoptosome formation and procaspase activation, they also highlight important evolutionary differences with functional implications for caspase activation. CARD/CARD interactions in the CED-4, Dark and Apaf-1 apoptosomes. Type I,IIand III interfaces that stabilize CARD-CARD interactions are indicated (left column). Note that the Type I interface appears to be unique to Apaf-1/pc-9 CARD interactions. Middle column shows cartoons of the active states of the CARD-CARD disks, illustrating the two CED-4 tetrameric ring layers (top) and the recruitment of 8 Dronc CARDs and between 3-4 pc-9 CARDs, to the Dark and Apaf-1 apoptosomes respectively (middle and lower panels). Ribbon diagrams of the CED-4, Dark and Apaf-1 apoptosomes are shown (right column).
[
Biol Bull,
1998]
In certain invertebrate muscles, adjacent narrow columns of sarcomeres are displaced along the fiber axis, providing an obliquely striated myofilament pattern in certain section planes. Although this architecture is described in many phyla and has been the subject of much discussion (1-12), its mechanical significance has yet to be resolved. In nematodes, where ultrastructural details of the obliquely striated muscle have long been known (12-19), another unique and prominent feature is the attachment of every sarcomere to the plasmalemma and basal lamina via dense bodies (Z-disc analogs). Unfortunately, the importance of this feature to the transmission of the contractile force to the cuticle is not understood outside the Caenorhabditis elegans literature: it was overlooked in recent reviews covering obliquely striated muscle (9-11). Here we consider transmission of force and oblique striation together. We compare the contractile architecture in C. elegans with that in the more complex muscle type of larger nematodes. Both types are designed to transmit the force of contraction laterally to the cuticle rather than longitudinally to the muscle ends. In the second type, folding of the contractile structure around an inward extension of the basal lamina enables a higher number of sarcomeres to be linked to cuticle per unit length. We suggest that the mechanical significance of the oblique arrangement of sarcomeres in both types is that it distributes the force application sites of the sarcomeres more evenly over the basal lamina and cuticle. With this muscle architecture, smooth bending of the nematode body tube would be possible, and kinking would be prevented.