The Laboratory of Dr. Joel Rosenbaum



Our Research


We use the bi-flagellate alga Chlamydomonas and the worm C. elegans to study the assembly and maintenance of motile and sensory cilia.

Bi-directional movement of multi-polypeptide particles underneath the flagellar membrane is called Intraflagellar Transport (IFT). It is required for the assembly and maintenance of all sensory and motile cilia and flagella, and is hypothesized to be the mechanism by which pre-assembled axonemal 9 + 2 precursors are moved out to their tip assembly sites, and also for the movement of proteins into the ciliary membranes. Anterograde movement is powered by kinesin-II, and the retrograde movement by cytoplasmic dynein 1b. IFT particles occur in chains of varying length that are attached to the overlying ciliary membrane and the B-subfiber of the outer doublet microtubules.

IFT was first observed by us in the flagella of the green alga, Chlamydomonas where it was shown that the particles are composed of two complexes, A and B, containing up to 16 polypeptides. Since its initial observation, IFT has been documented in sea urchin cilia, the mechanosensory cilia of Drosophila and vertebrate primary cilia including the connecting cilia of the rods and cones, and the cilia of collecting tubule cells in the kidney. In our laboratory IFT has been visualized directly in the sensory cilia of C. elegans by use of GFP-tagged constructs of IFT genes.

Mutations affecting IFT in vertebrates have been linked to Polycystic Kidney Disease (PKD), and Tg737 KO mice with autosomal recessive PKD have a defect in IFT and lack normal primary cilia in the kidney. In C. elegans, homologues of the polycystins, the calcium dependent cation channel polypepides which are defective in PKD, are localized on the primary sensory cilia. It is hypothesized from this that vertebrate PKD can result if the primary cilia are no longer present or abnormal so that the polycystins cannot be targeted to the ciliary membranes.

Defects in IFT in vertebrates have also been shown to cause lack of the cilia on nodal cells in the mouse (Henson's node in chick). If the nodal cilia are abnormal, or are unable to rotate, situs inversus results, i.e. vertebrate developmental asymmetry of organ placement on the right vs. left side of the midline.

The IFT particles reach the flagellar tip by means of kinesin, drop their cargo, pick up flagellar turnover products at the tip, and return to the flagellar base by means of cytoplasmic dynein. We are isolating the proteins at the tip of the flagellum where all of this activity takes place, including EB1. Mutants have been generated which are defective in tip (microtubule plus end) activities.

Since primary cilia are present on almost all vertebrate cells, it is quite possible that the membranes of these cilia are repositories for specific ion channels (e.g. polycystins) and receptors. For example, in the vertebrate brain, certain somatostatin receptors are localized only on the primary cilia membranes in a variety of brain cells. We are cloning and sequencing the genes for various flagellar membrane proteins, including PKD-2, to determine how they are moved to the flagellar membrane, and how their amounts on the membrane are controlled.




Joel Rosenbaum

Professor Molecular, Cellular and Developmental Biology

Principle Investigator

Dennis Diener

Associate Research Scientist

Kaiyao Huang

Postdoctoral Fellow

Che-Chia Tsao

Postdoctoral Associate

Christopher R. Wood

Postdoctoral Fellow

Hue Tran

Laboratory Assistant

Laudiceia Vincent

Laboratory Assistant