QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Summary Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ikeda, A. Articles by Naggert, J. K. Search for Related Content PubMed PubMed Citation Articles by Ikeda, A. Articles by Naggert, J. K.

The tubby-like proteins, a family with roles in neuronal development and function

The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA

View larger version (17K): [in a new window]   Fig. 1. Organization of the TUB, TULP3 and TULP1 proteins. Each box represents amino acids translated from each exon, and the percentage amino-acid sequence similarity with TUB is shown. Green boxes indicate the N-terminal regions with relatively low homology between family members. Red boxes indicate the C-terminal regions with high homology. The blue boxes represent the common acceptor site for alternative N-terminal exons observed in both human and mouse TUB. Yellow and pink boxes represent exons that are not conserved among family members. The nuclear localization signal is indicated. The N-terminal regions of TUB and TULP1 are able to activate transcription; the C-terminal region of TUB can bind to double-stranded DNA and to phosphatidylinositol-phosphates.

View larger version (40K): [in a new window]   Fig. 2. Proposed molecular functions of TULPs. (a) TUB as a mediator of insulin signaling. TUB is phosphorylated by the insulin receptor kinase domain, as well as by ABL and JAK2. This phosphorylation increases the binding capacity of TUB for proteins that have SH2 domains, such as PLC-. (b) TUB as a nuclear signaling molecule. TUB is attached to the plasma membrane through PtdIns(4,5)P2. The signals from G-protein-coupled receptors phosphorylate Gq and release TUB through PLC-ß activity. TUB released from the plasma membrane is translocated to the nucleus where it may act as a transcription factor. (c) TUB as a facilitator of rhodopsin transport in rod photoreceptors. The rod photoreceptor structure has five distinct components: the rod outer segment (OS) containing membrane discs stacked within a plasma membrane envelope; the inner segment (IS) containing the biosynthetic machinery; the connecting cilium (CC) joining the OS and IS; the cell body containing the nucleus; and the spherule representing the synaptic ending of the cell (Tai et al., 1999). Rhodopsin is manufactured in the Golgi apparatus of the IS and packaged into vesicles. The C-terminal tail of opsin interacts with the dynein light chain and is transported along microtubules to the cilium where the rhodopsin-containing vesicles fuse with the plasma membrane. Rhodopsin is then thought to be transported to the outer segment (blue arrows) by kinesin-II (Tai et al., 1999; Marszalek et al., 2000). In Tulp1–/– mice, mislocalization of rhodopsin is observed in the plasma membrane (red arrows). Since TULP1 is localized in the IS, it may be involved in the transport the vesicles containing rhodopsin.