<Li> Formation of membrane protrusions: Some cell types, under specific conditions, may develop different types of long, thin extensions of the cell membrane called membrane protrusions . Three types have been described: microtubule spikes, apoptopodia (feet of death), and beaded apoptopodia (the latter having a beads - on - a-string appearance). Pannexin 1 is an important component of membrane channels involved in the formation of apoptopodia and beaded apoptopodia . </Li> <Li> Fragmentation: The cell breaks apart into multiple vesicles called apoptotic bodies, which undergo phagocytosis . The plasma membrane protrusions may help bring apoptotic bodies closer to phagocytes . </Li> <P> The removal of dead cells by neighboring phagocytic cells has been termed efferocytosis . Dying cells that undergo the final stages of apoptosis display phagocytotic molecules, such as phosphatidylserine, on their cell surface . Phosphatidylserine is normally found on the inner leaflet surface of the plasma membrane, but is redistributed during apoptosis to the extracellular surface by a protein known as scramblase . These molecules mark the cell for phagocytosis by cells possessing the appropriate receptors, such as macrophages . The removal of dying cells by phagocytes occurs in an orderly manner without eliciting an inflammatory response . During apoptosis cellular RNA and DNA are separated from each other and sorted to different apoptotic bodies; separation of RNA is initiated as nucleolar segregation . </P> <P> Many knock - outs have been made in the apoptosis pathways to test the function of each of the proteins . Several caspases, in addition to APAF1 and FADD, have been mutated to determine the new phenotype . In order to create a tumor necrosis factor (TNF) knockout, an exon containing the nucleotides 3704--5364 was removed from the gene . This exon encodes a portion of the mature TNF domain, as well as the leader sequence, which is a highly conserved region necessary for proper intracellular processing . TNF - / - mice develop normally and have no gross structural or morphological abnormalities . However, upon immunization with SRBC (sheep red blood cells), these mice demonstrated a deficiency in the maturation of an antibody response; they were able to generate normal levels of IgM, but could not develop specific IgG levels . Apaf - 1 is the protein that turns on caspase 9 by cleavage to begin the caspase cascade that leads to apoptosis . Since a - / - mutation in the APAF - 1 gene is embryonic lethal, a gene trap strategy was used in order to generate an APAF - 1 - / - mouse . This assay is used to disrupt gene function by creating an intragenic gene fusion . When an APAF - 1 gene trap is introduced into cells, many morphological changes occur, such as spina bifida, the persistence of interdigital webs, and open brain . In addition, after embryonic day 12.5, the brain of the embryos showed several structural changes . APAF - 1 cells are protected from apoptosis stimuli such as irradiation . A BAX - 1 knock - out mouse exhibits normal forebrain formation and a decreased programmed cell death in some neuronal populations and in the spinal cord, leading to an increase in motor neurons . </P>

Apoptotic bodies are phagocytized without the process of