In fact, recent studies in nonneuronal cells indicate an expanding repertoire of cellular functions for ORC subunits. One might logically ask how the nuclear function of the ORC in binding DNA and regulating replication initiation could relate to a cytosolic function in dendrite growth and morphogenesis. Importantly, the function of the ORC is tightly regulated during the cell cycle by cyclin-dependent kinase (Cdk) activity and by ATPase-dependent changes in subunit conformation and modification ( Bell, 2002). In addition, the ORC prevents replication reinitiation to ensure single copy genome duplication. The ORC initiates the assembly of a prereplication complex in part by binding the accessory proteins CDC-6 and CDT-1, which are essential for coating the DNA with MCM proteins, a requisite step in replication. Among these subunits, three (Orc1, Orc4, and Orc5) belong to the AAA family of ATPases. The mammalian ORC is a hexameric protein complex composed of four core subunits (Orc2–5) and two peripheral subunits (Orc1 and Orc6) that together participate in initiating DNA replication during G1-S transition ( Bell and Stillman, 1992 Bell, 2002 Fig. What is the origin recognition complex (ORC)? “Origin” in this case refers to the origins of DNA replication present in all eukaryotic chromosomes ( Bell, 2002). In the current issue, a paper from the laboratory of Louis Reichardt identifies the origin recognition complex (ORC) as a molecular mischief maker regulating the development of dendrites and spines (see Huang et al. Now, barging from behind the curtain to interrupt this comfortable dialog is a most peculiar Puck of a protein.
Emerging from this basic script have been a cast of molecular characters including growth factors, actin regulatory proteins, postsynaptic density proteins, and transcription factors, whose presence onstage seems wholly justified and satisfying. As the dendrites continue their growth, actin-rich membrane protrusions appear over their surface, which contact axons and differentiate into micron-sized mushroom-shaped spines (specialized compartments housing neurotransmitter receptors and other requisite machinery for postsynaptic signaling Segal, 2005).
As dendrites grow, branches are thought to arise from extended filopodia, which are stabilized by making synaptic contact with nearby axons ( Niell et al., 2004). Quite understandably, studies to date have focused on the cytoskeletal changes and signaling events that determine how dendrites achieve their shape ( Jan and Jan, 2003).
0 kommentar(er)
