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CRUMBS > Current Knowledge > CRB1 function

Function of the CRB1 protein

In the human retina, the CRB1 protein is located at specific sites of photoreceptor cells, i.e. the inner segments (Figure 4). Both cone and rod photoreceptors consist of a synapse connecting with neuronal cells, a nuclear body containing the nucleus, an inner segment, and an outer segment containing the principle photon-capturing molecules, rhodopsin in rod photoreceptors and blue, red and green opsins in cone photoreceptor cells. CRB1 is positioned in a belt-like structure of the inner segments where it is believed to function in the maintenance of cell polarity of the photoreceptors (van de Pavert et al., 2004). As CRB1 is inserted through the cell membrane, it probably serves important functions both inside and outside the photoreceptor cell. Inside the cell, the 37-amino acid segment is known to act as an anchor for several proteins, such as MPP5 or PALS1 (Roh et al., 2002). The consortium showed that MPP5 itself can interact with other proteins such as MUPP1 and MPP4 and in this way a complex network of proteins is situated at this position (Kantardzhieva et al., in press; Meuleman et al., 2004; van de Pavert et al., 2004). Research is ongoing to elucidate the precise function of the much larger extracellular part (1347 amino acids).

 Localization of the CRB1 protein.

Figure 4: Localization of the CRB1 protein. A. Schematic picture of a selection of the different cell types of the retina and schematic illustration of two photoreceptor cells adjacent to Müller cells and the location of CRB1. B. Schematic representation of proteins at the outer limiting membrane (van de Pavert et al. 2004). C. Immunolocalization of the CRB1 protein at the outer limiting membrane. The CRB1 protein is located in a belt-like configuration of the photoreceptor inner segments, between photoreceptor cells and Müller cells (van de Pavert et al. 2004). Abbreviations: RPE, retinal pigment epithelium; PCL, photoreceptor cell layer; ONL, outer nuclear layer; OPL, outer plexiform layer; OLM, outer limiting membrane; INL, innner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer.

Typical features of retina morphology in human patients

Dr. S. Jacobson and coworkers employed a novel method (ocular coherence tomography) to visualize the structure of the retina in patients. Surprisingly, they found that patients with congenital blindness and CRB1 mutations had a relatively thick retina in contrast to patients with mutations in other genes which in most cases show a thinning of the retina (Jacobson et al. 2003). Hence, this novel technique might be employed to identify patients with congenital blindness and CRB1 mutations. This result also means that cell death is not likely the underlying cause of CRB1-associated blindness. Retinal thickening was not observed in the mice with a Crb1 mutation.