PDGFRB (platelet-derived growth factor receptor, beta polypeptide)

5q32

PDGFRB is made of five extracellular immunoglobulin loops, a transmembrane domain and a split intracellular kinase domain. PDGFA, PDGFB, PDGFC, and PDGFD form homo or heterodimers to bind PDGFRA and PDGFRB, inducing their dimerization and transduction of the signal to several signaling pathways (RAS/RAF/MAPK, PI3K/AKT/mTOR, PLCG and other pathways) involved in multiple cellular and developmental responses. PDGFRB signaling is particularly important in blood vessel formation and early hematopoiesis (review in Andrae et al., 2008). PDGFRB is a well known partner in different translocations found in chronic myeloproliferative disorders, myelodysplastic/myeloproliferative syndromes, and acute myeloid leukemias (Vizmanos 2005). There is high PDGFRB expression in metastatic medulloblastoma (Gilbertson and Clifford, 2003), chordoma (Tamborini et al., 2006), malignant peripheral nerve sheath tumor (Aoki et al., 2007), and in sarcomatoid non-small cell lung cancer (Tsao et al., 2011).

NDE1 (nudE neurodevelopment protein 1)

16p13.11

NDE1 is made of a N-terminal coiled-coil domain (self-association), dynein-binding domains, a domain interacting with PAFAH1B1, a region interacting with CENPF, a predicted disordered region that allows a bent back structure, and a C-terminal helix. This facilitates interaction of the C-terminal region with the N-terminal coiled-coil domain, homo or heterodimerization with NDEL1 and dynein interaction. NDE1, NDEL1 and PAFAH1B1 (LIS1) are DISC1 interactors. NDE1 plays a crucial role in microtubule organization and cell cycle progression, and is required for neuronal development. NDE1 localizes to the centrosome and mitotic spindle poles. Essential role in the cytoskeleton dynamics (mitosis, nuclei positioning, and cell migration) (review in Soares et al., 2012). NDE1 has been found to localise to the post-synaptic density. NDE1 plays an essential role in human cerebral cortex neurogenesis. Homozygous frameshift mutations in NDE1 was found in families with microlissencephaly, massive reduction in neuron numbers, and profound mental retardation; parents were unaffected (no heterozygote effects) (Bakircioglu et al., 2011; Alkuraya et al., 2011). Deletions and duplications at chromosomal 16p13.1, containing the NDE1 gene, are significantly over-represented in schizophrenia patients. Positive genetic association studies have been reported indicating that NDE1 and other DISC1 interactors may be implicated in schizophrenia (review in Bradshaw and Porteous, 2012). Of note, is that MYH11 and NDE1 are transcribed from overlapping opposing DNA strands, and, consequently, NDE1 is disrupted in 90% of cases with acute myeloid leukemia and inv(16)(p13q22) (Van der Reijden et al., 2010).