Short interfering RNAs (siRNAs) and microRNAs (miRNAs) are both processed from longer, double-stranded RNA (dsRNA) presursors by a member of the Dicer (Dcr) family of proteins. siRNAs generally arise from perfectly base-paired dsRNAs, whereas miRNAs are excised from 60-70 nt pre-miRNA hairpins containing multiple bulges and mismatches within the duplexed...
The formation of a primary endocytic vesicle bud is a dynamic process involving the transient organization of adaptor and scaffold proteins at the plasma membrane. The proteins involved in early endocytosis have modular protein interaction motifs and domains that are predicted to contribute to scaffold formation. These motifs are found...
To maintain polarity, epithelial cells continuously sort transmembrane proteins to the apical or basolateral membrane domains during biosynthetic delivery or after internalization. This thesis was designed to elucidate the molecular mechanism underlying protein trafficking. Our studies identified Rab13 as a critical GTPase regulator of biosynthetic cargos that are transported from...
In male mammals, testosterone (T) is critical for sexual differentiation during development and reproductive success in adulthood. This thesis examines the cellular and molecular processes that mediate T's actions in the male brain and reproductive axis. Although T is clearly necessary for sexual behavior, the cellular mechanisms by which it...
Rsp5 is a ubiquitin ligase that controls a broad range of cellular processes in budding yeast and is part of a large family of proteins that controls analogous processes in mammalian cells. Although Rsp5 targets a number of different substrates for ubiquitination, the mechanisms that regulate Rsp5 catalytic activity are...
Assembly of the large and small subunits of the <em>E. coli</em> ribosome is a complicated process that involves transcription, processing, and modifying of the ribosomal RNA, the binding of ribosomal proteins, and the folding of the particles into complex structures. A number of ribosome assembly factors, including maturation factors, GTPases,...
Polarized epithelial cells are divided by tight junctions into an apical membrane domain, which faces the lumen of an organ, and a basolateral domain, which is in contact with underlying connective tissues. To establish and maintain polarity, newly synthesized and recycling transmembrane proteins are sorted to either the apical or...
A pyramidal neuron receives thousands of inputs spread throughout its dendritic tree, which it must integrate into a decision about whether or not to fire action-potential output. Since action potentials are the primary means by which these neurons communicate with their network partners, understanding this input-output relationship is critical for...
Since its discovery, RNA interference (RNAi) has become a powerful tool used in laboratories to understand developmental processes, and it is now commonly used to investigate gene function. Using RNAi, scientists can routinely knock out specific genes to prevent their expression, observe its phenotypes, and then help determine the function...
Eukaryotic gene transcription is a coordinated process involving the participation of a large number of proteins. Sequence-specific DNA-binding transcription factors function as activators or repressors of transcription and frequently recruit transcriptional coregulators that lack specific DNA-binding activity. These multi-protein complexes with intrinsic chromatin-modifying and chromatin-remodeling activities have emerged as key...