Novel structure found in ‘antennae’ of light-sensing neurons
Perseverance and high-resolution techniques helped uncover a biological mystery
Using state-of-the-art super-resolution microscopy (STORM) coupled with cryo-electron tomography and genetic models, the researchers discovered that when SPATA7 was present, SPATA7-binding proteins localized throughout the connecting cilium. But in the absence of SPATA7, the binding proteins concentrated at the base of the cilium in a region closest to the body of the neuron, the researchers called it the proximal region, leaving a distal region empty of SPATA7-binding proteins. Chen, Dharmat and their colleagues also observed that proteins that did not bind to SPATA7 always localized in the proximal region, both when SPATA7 was present and absent.
This suggested a new concept; that there are two distinct regions within the connecting cilium of photoreceptors. One is the proximal zone, where all ciliary proteins reside. The other region is the distal region, where SPATA7-binding proteins localize when SPATA7 is available. The researchers hypothesized that SPATA7 either takes the proteins to the distal region or is required to maintain them there, thereby supporting a long, elaborate connecting cilium structure unique to photoreceptors.
Additional experiments showed that the absence of SPATA7 disrupts protein localization and the stability of microtubules, structures that provide structural integrity to the cilia, specifically in the distal region of the connecting cilium.
“Cilia in other cell types also have SPATA7, but these cilia do not have a distal region in the transition zone like the one we discovered in cilia of photoreceptors, therefore they are not affected when SPATA7 is mutated,” Dharmat said.
“The presence of this unique distal zone exclusively in the cilia of photoreceptors also explains the biological mystery of non-syndromic blindness observed in both patients and mouse models, that loss of certain transition zone proteins only causes degeneration of cilia in photoreceptors without affecting the cilia on other cell types,” Dharmat said.
This research brings to light a novel sub-cellular structure in the cilium of photoreceptors, its biochemical components and its impact on the function of the cilia, all of which contribute to a better understanding of both genetic disorders and the structure of cilia in the retina.
Other contributors to this work include Aiden Eblimit, Michael A. Robichaux, Zhixian Zhang, Thanh-Minh T. Nguyen, Sung Yun Jung, Feng He, Antrix Jain, Yumei Li, Jun 4 Qin, Paul Overbeek, Ronald Roepman, Graeme Mardon and Theodore G Wensel. The authors are affiliated with Baylor College of Medicine or Radboud University Medical Center, The Netherlands.
This project was funded by the Retina Research Foundation, National Eye Institute R01EY022356, R01EY020540, R01-EY026545, R01-EY07981 and F32EY027171. Support was also provided by the European Community's Seventh Framework Programmes FP7/2009 under grant agreement no: 241955 684 (SYSCILIA) and by the Netherlands Organization for Scientific Research 685 (NWO Vici-865.12.005).