Cellular and molecular biology of optineurin - PubMed (original) (raw)

Review

Cellular and molecular biology of optineurin

Hongyu Ying et al. Int Rev Cell Mol Biol. 2012.

Abstract

Optineurin is a gene linked to glaucoma, amyotrophic lateral sclerosis, other neurodegenerative diseases, and Paget's disease of bone. This review describes the characteristics of optineurin and summarizes the cellular and molecular biology investigations conducted so far on optineurin. Data from a number of laboratories indicate that optineurin is a cytosolic protein containing 577 amino acid residues. Interacting with proteins such as myosin VI, Rab8, huntingtin, transferrin receptor, and TANK-binding kinase 1, optineurin is involved in basic cellular functions including protein trafficking, maintenance of the Golgi apparatus, as well as NF-κB pathway, antiviral, and antibacteria signaling. Mutation or alteration of homeostasis of optineurin (such as overexpression or knockdown) results in adverse consequences in the cells, leading to the development of neurodegenerative diseases including glaucoma.

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Figures

Figure 5.1

Sequence alignment of optineurin protein from human, chimpanzee, cow, dog, rat, mouse, chicken, and zebrafish. Multiple sequence alignment is generated by ClustalW2 (

http://www.ebi.ac.uk/msa/clustaw2/

Figure 5.2

Phylogenetic tree to show the distance of optineurin protein between different species. Phylogenetic tree is generated by ClustalW2 (

http://www.ebi.ac.uk/msa/clustaw2/

Figure 5.3

(A) Schematic representation of human optineurin protein domains and the binding sites of optineurin-interacting proteins. CC, coiled-coil; LZ, leucine zipper domain; LIR, LC3 interacting motif; UBD, ubiquitin-binding domain; ZnF, zinc finger; aa, amino acid. (B) Optineurin mutations associated with glaucoma and ALS. Note that L157A is not disease associated but rather is a mutation used in the study to affect the leucine zipper domain. D474N also is not a disease associated mutation. It was used in studies to abolish ubiquitin binding. (For color version of this figure, the reader is referred to the Web version of this chapter.)

Figure 5.4

Schematic model illustrating how optineurin may coordinate actin cytoskeleton and microtubule system for maintenance of the Golgi complex by interacting with various binding partners (modified from Sahlender et al., 2005 with updates). The C-terminal of optineurin binds with Htt which has been shown to bind with HAP1. HAP1 interacts with the plus (+)-end-directed microtubule motor protein dynein as well as dynein activator dynactin. The minus (−)-end-directed microtubule motor kinesin interacts with Htt and HAP1. Optineurin links Rab8 with myosin VI which is an actin-based motor protein. In scenarios of optineurin deletion or overexpression, the interaction between optineurin and its binding partners (such as myosin VI, Rab8, and Htt) may be altered and the balance between the motor proteins may be disturbed to induce fragmentation of the Golgi complex. (For color version of this figure, the reader is referred to the Web version of this chapter.)

References

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Cellular and molecular biology of optineurin - PubMed (original) (raw)