To define the poorly understood mechanisms by which IE1 achieves its diverse functions, we identified IE1 domains that contribute to productive infection of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), the baculovirus prototype. Site-directed mutagenesis revealed that the N-terminal 23 residues of IE1 are required for origin-specific DNA replication and AcMNPV propagation, but not for DNA-binding-dependent transcriptional activation. Within this defined replication domain, we identified an invariant TPXR/H motif that resembles a consensus cyclin-dependent kinase phosphorylation site. Amino acid substitutions of potential phosphorylation sites within

or near this motif caused LY2090314 loss of IE1-mediated learn more DNA replication activity. Remarkably, substitution of the single threonine (residue 15) within the TPXR/H motif caused complete loss of AcMNPV multiplication. The replication domain was required for

IE1 phosphorylation. It was also sufficient for conferring phosphorylation of a heterologous protein. Importantly, IE1 hyperphosphorylation coincided exclusively with AcMNPV DNA replication. The temporal regulation of IE1 phosphorylation and the essential nature of the TPXR/H motif suggest that phosphorylation critically alters and possibly activates DNA replication activity of IE1 during infection. The striking conservation of the TPXR/H motif among IE1 proteins

further suggests that this molecular switch may be a common mechanism by which the alphabaculoviruses coordinate DNA replication and gene expression by using a single regulator.”
“Drugs of abuse have acute and persistent effects on synapse structure and addiction-related behaviors. Trans-synaptic interactions can mTOR activator control synapse development, and synaptic cell adhesion molecule (SynCAM) proteins (also named nectin-like molecules) are immunoglobulin adhesion proteins that span the synaptic cleft and induce excitatory synapses. Our studies now reveal that the loss of SynCAM 1 in knockout (KO) mice reduces excitatory synapse number in nucleus accumbens (NAc). SynCAM 1 additionally contributes to the structural remodeling of NAc synapses in response to the psychostimulant cocaine. Specifically, we find that cocaine administration increases the density of stubby spines on medium spiny neurons in NAc, and that maintaining this increase requires SynCAM 1. Furthermore, mushroom-type spines on these neurons are structurally more plastic when SynCAM 1 is absent, and challenging drug-withdrawn mice with cocaine shortens these spines in SynCAM 1 KO mice. These effects are correlated with changes on the behavioral level, where SynCAM 1 contributes to the psychostimulant effects of cocaine as measured after acute and repeated administration, and in drug-withdrawn mice.