Programmed cell death 10 protein (PDCD10/CCM3) is part of the CCM complex and is required for neuronal migration []. Outside of this complex, it is crucial in vascularization and in angiogenesis as it functions in vessel permeability and stability []. This protein plays an essential role in early embryonic angiogenesis and cardiovascular development. PDCD10/CCM3 interacts with a variety of proteins, including paxillin, membrane receptor vascular epidermal growth factor receptor 2, CCM complex component CCM2 and germinal centre kinase III proteins (GCKIII). PDCD10/CCM3 contains an N-terminal dimerisation domain and a C-terminal focal adhesion targeting-homology (FAT-H) domain [, , ].This entry represents the N-terminal dimerisation domain of PDC10/CCM3, consisting of four α-helices. This domain is also found at the C-terminal of GCKIIIs (STK24/MST3, STK25, STK26/MST4), which adopts a closely related fold. GCKIIIs are involved in the regulation of apoptosis, cell proliferation, polarity, migration, and cytoskeleton remodelling. This domain mediates homo and heterodimerization. PDCD10/CCM3 forms a heterodimer with GCKIIIs analogous to CCM3 homodimer [, ].
Programmed cell death 10 protein (PDCD10/CCM3) is part of the CCM complex and is required for neuronal migration []. It also has roles outside of this complex [], it is crucial in vascularization and in angiogenesis as it functions in vessel permeability and stability []. PDCD10/CCM3 was originally discovered to be upregulated during granulocyte apoptosis and is thought to play a role in cell death []. However, a specific role for PDCD10 in cell survival is not clear as both pro-survival and pro-apoptotic effects have been reported [, ]. PDCD10/CCM3 contains an N-terminal dimerisation domain and a C-terminal focal adhesion targeting-homology (FAT-H) domain [].There are three CCM proteins: CCM1 (also known as KRIT1), CCM2 (also known as OSM and malcavernin) and CCM3 (also known as PDCD10). Mutations in the genes encoding CCM proteins cause cerebral cavernous malformations (CCMs), a disease characterised by dilated leaky blood vessels, especially in the neurovasculature, that result in increased risk of stroke, focal neurological defects and seizures. The CCM proteins can form a trimeric complex. They can also interact with a range of signaling, cytoskeletal and adaptor proteins that may account for their roles in a range of basic cellular processes including cell adhesion, migration, polarity and apoptosis [].
