June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Photoreceptor-specific transition zone (PSTZ), a novel sub-region of the connecting cilium (CC), is maintained by retinal ciliopathy protein SPATA7.
Author Affiliations & Notes
  • Rachayata Dharmat
    Molecular and Human Genetics, Baylor college of medicine, Houston, Texas, United States
    HGSC, Baylor College of Medicine, Houston, Texas, United States
  • Aiden Eblimit
    HGSC, Baylor College of Medicine, Houston, Texas, United States
  • Yumei Li
    HGSC, Baylor College of Medicine, Houston, Texas, United States
  • Michael Robichaux
    Dept of Biochemistry, Baylor College of Medicine, Houston, Texas, United States
  • Zhixian Zhang
    Dept of Biochemistry, Baylor College of Medicine, Houston, Texas, United States
  • Feng He
    Dept of Biochemistry, Baylor College of Medicine, Houston, Texas, United States
  • Antrix Jain
    Dept of Biochemistry, Baylor College of Medicine, Houston, Texas, United States
  • Graeme Mardon
    Molecular and Human Genetics, Baylor college of medicine, Houston, Texas, United States
  • Sung Yun Jung
    Dept of Biochemistry, Baylor College of Medicine, Houston, Texas, United States
  • Theodore G Wensel
    Dept of Biochemistry, Baylor College of Medicine, Houston, Texas, United States
  • Rui Chen
    Molecular and Human Genetics, Baylor college of medicine, Houston, Texas, United States
    HGSC, Baylor College of Medicine, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Rachayata Dharmat, None; Aiden Eblimit, None; Yumei Li, None; Michael Robichaux, None; Zhixian Zhang, None; Feng He, None; Antrix Jain, None; Graeme Mardon, None; Sung Yun Jung, None; Theodore Wensel, None; Rui Chen, None
  • Footnotes
    Support  Grants from National Eye Institute (R01EY022356) and Retinal Research Foundation to R.C
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2485. doi:
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      Rachayata Dharmat, Aiden Eblimit, Yumei Li, Michael Robichaux, Zhixian Zhang, Feng He, Antrix Jain, Graeme Mardon, Sung Yun Jung, Theodore G Wensel, Rui Chen; Photoreceptor-specific transition zone (PSTZ), a novel sub-region of the connecting cilium (CC), is maintained by retinal ciliopathy protein SPATA7.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2485.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : A hallmark of the photoreceptor sensory cilium is the presence of a specialized structural homolog of transition zone called the connecting cilium (CC). Interestingly, certain transition zone genes, such as SPATA7, specifically impairs the function of the CC without affecting the transition zone of primary cilia when mutated. To determine how the CC is functionally distinct from the transition zone, we investigated the impact of the loss of a photoreceptor-specific ciliary protein to probe the differences between the CC and the transition zone using Spata7 KO mice as the model.

Methods : To understand the function of SPATA7 at the CC, we performed IP-MS based proteomic profiling to identify SPATA7-interacting proteins. We next assessed the localization of interacting partners in the absence of Spata7 and Sdccag8 using immunohistofluorescence and confirmed it using super-resolution STORM microscopy on the photoreceptors of P15 Spata7 KO mice. Since we observed morphological defects, we further assessed structural alterations of the microtubules using cryo-tomography.

Results : SPATA7 interacts with the RPGR and NPHP complex and localizes throughout the length of the CC. In the absence of SPATA7, its interacting proteins are specifically absent (or excluded) from the distal CC which we named the photoreceptor-specific transition zone (“PSTZ”). However, the localization of CC proteins in the proximal CC (pCC) remains unaffected. In contrast, this peculiar phenotype is not observed in the absence of a pCC protein, SDCCAG8. Functionally, the PSTZ complex is important for stabilization of the CC structure as its absence leads to destabilization of ciliary microtubules specifically in the distal CC. This destabilization is caused due to the absence of CEP290, from the PSTZ region, a component of Y-links that are essential for the integrity of microtubules.

Conclusions : Our data displays a novel photoreceptor-specific sub-region in the distal CC, termed the PSTZ, which plays a critical role in the functioning of the CC. Cilia-related proteins at the PSTZ are essential for maintaining the integrity of the microtubule core thereby stabilizing the CC. Hence we propose that this unique PSTZ region makes the CC functionally and structurally distinct from the transition zone found in other primary cilia.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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