Group Andreas Gießl

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Cilia in Sensory Systems

Issue

The focus of our research is to investigate the function of vertebrate photoreceptor cells and other cilia containing sensory systems. The main interests are the basic cellular mechanisms by which cytoskeletal elements and protein complexes work together to regulate the distribution of molecules in the morphologically and functionally distinct compartments of the sensory cells.

Focus

Vertebrate Photoreceptor Cells

In the vertebrate retina, the light sensitive outer segment of the photoreceptor is linked via a small intracellular bridge, the connecting cilium, with the inner segment. The inner segment contains the typical energy producing and protein synthesizing components of an eukaryotic cell. The abundant membrane turnover in the outer segment requires an efficient and massive transport of all disc components from the nuclear region and the inner segment to the place of signal transduction. All molecules have to traffic from the synthesizing organelles of the nuclear and inner segment region, through the connecting cilium to their destination in the outer segment. The connecting cilium is a modified and specialized, non-motile primary cilium, containing the whole transport network and the passage between the inner and outer segment with roads in both directions and a traffic control system for the different cargos.

Possible role of pericentrin (Pcnt) in the ciliary transport in photoreceptor cells

Pericentrin – also known in human as kendrin – is one of the best-studied mammalian centrosomal proteins. Several spliced transcripts are encoded from one orthologous gene in mice and human, and pericentrin is characterized by coiled-coil domains throughout most of its structure and a PCM (peri-centrosomal-matrix) targeting motif called the PACT domain near its carboxyl terminus. We found with immunocytochemistry and high-resolution light microscopical analyses that pericentrin and several interacting partners, known from the centrosome, localize to the basal body and the centriole of the connecting cilium. Here they co-localize with the entire protein transport machinery from the inner to the outer segment of photoreceptor cells. Studying pericentrin function may help us to understand the regulation of protein transport in photoreceptor cells and provide new insights into human disorders related to defects in ciliary function.

Possible role of the kinase Nek1 in the ciliary development in sensory neurons

In collaboration with PD Dr. med. Christian Thiel (human genetics, Erlangen) we identified mutations in a gene called NEK1 (NIMA-related serine/threonine kinase) to cause the human short-rib polydactyly syndrome Majewski type. We could show that loss-of-function-mutations in the NEK1 gene severely reduce cilia number and alter ciliary morphology in a patient-derived fibroblast cell line. Many genes of syndromic ciliopathies are coding for components of the cilium or the basal body complex and play a role in protein selection and transport in or along the cilium. Mutations in genes encoding ciliary proteins are mostly result in a degeneration of the whole ciliary complex. We think that the investigation of the function of the kinase Nek1 would bring new consolidated insights to understand more about ciliopathic human genetic disorders.

Methods

In our experimental approach, we combine neuroanatomical, immunocytochemical, biochemical, molecular, cell biological and physiological methods to investigate the retinae of wildtype, mutant, and transgenic mice.

Video about our work in Erlangen

Collaborations