A defined tubby domain β-barrel surface region of TULP3 mediates ciliary trafficking of diverse cargoes.

The primary cilium is a paradigmatic subcellular compartment at the nexus of numerous cellular and morphogenetic pathways. The tubby family protein TULP3 acts as an adapter of the intraflagellar transport complex A in transporting integral membrane and membrane-associated lipidated proteins into cilia. However, the mechanisms by which TULP3 coordinates ciliary transport of diverse cargoes is not well understood.

Tubb4b is required for multi-ciliogenesis in the mouse.

Cilia are microtubule (MT)-based organelles present on the surface of nearly all vertebrate cells. MTs are polymers of α- and β-tubulins that are each encoded by multiple, individual isotype genes. Tubulin isotype composition is thought to influence MT behaviors.

Interactions between TULP3 tubby domain and ARL13B amphipathic helix promote lipidated protein transport to cilia.

The primary cilium is a nexus for cell signaling and relies on specific protein trafficking for function. The tubby family protein TULP3 transports integral membrane proteins into cilia through interactions with the intraflagellar transport complex-A (IFT-A) and phosphoinositides. It was previously shown that short motifs called ciliary localization sequences (CLSs) are necessary and sufficient for TULP3-dependent ciliary trafficking of transmembrane cargoes.

A dominant tubulin mutation causes cerebellar neurodegeneration in a genetic model of tubulinopathy.

Mutations in tubulins cause distinct neurodevelopmental and degenerative diseases termed "tubulinopathies"; however, little is known about the functional requirements of tubulins or how mutations cause cell-specific pathologies. Here, we identify a mutation in the gene that causes degeneration of cerebellar granule neurons and myelination defects. We show that the neural phenotypes result from a cell type-specific enrichment of a dominant mutant form of relative to the expression other β-tubulin isotypes.

Mutations in Ciliary Trafficking Genes affect Sonic Hedgehog-dependent Neural Tube Patterning Differentially along the Anterior-Posterior Axis.

Cell specification in the ventral spinal cord is a well-studied model system to understand how tissue pattern develops in response to a morphogen gradient. Ventral cell types including motor neurons (MNs) are induced in the neural tube in response to graded Sonic Hedgehog (Shh) signaling. We performed a forward genetic screen in the mouse that incorporated a GFP-expressing transgene to visualize MNs to identify genes regulating ventral patterning.