The major goal of the Imanishi lab is to understand the molecular basis of protein transport and membrane morphogenesis in photoreceptor neurons. Deficiencies in these processes lead to photoreceptor degenerative disorders. By combining imaging and molecular biology methods, we  aspire to solve long standing questions regarding the mechanism of photoreceptor degeneration caused by mislocalized rhodopsin. Another critical goal of the laboratory is to develop novel therapeutic strategies for treating inherited blinding disorders.

To accomplish these goals, Imanishi lab focuses on the following areas of research: (1) Morphogenesis and maintenance of membrane structures in photoreceptor neurons; (2) Ciliary protein trafficking and ciliopathy in the retina; (3) Drug discovery for inherited blinding disorders. We apply state of the art imaging technologies such as super-resolution fluorescence microscopy, multiphoton microscopy, and high-contents/high-throughout confocal microscopy to visualize and study the dynamic cellular processes. Moreover, we develop new technologies  to study proteome in photoreceptor and other retinal neurons at previously unprecedented spatiotemporal resolution.

RPE cells engulf microvesicles secreted by degenerating rod photoreceptors. Ropelewski P and Imanishi Y eNeuro 6 May 2020, ENEURO.0507-19.2020; DOI: https://doi.org/10.1523/ENEURO.0507-19.2020

Disrupted plasma membrane protein homeostasis in a Xenopus laevis model of retinitis pigmentosa. Ropelewski P and Imanishi Y J Neurosci. 2019 Jul 10;39(28):5581-5593. doi: 10.1523/JNEUROSCI.3025-18.2019.

Müller glia phagocytose dead photoreceptor cells in a mouse model of retinal degenerative disease. Sakami S, Imanishi Y*, Palczewski K*. The FASEB Journal. FASEB J. 2019 Mar;33(3):3680-3692. doi: 10.1096/fj.201801662R. (* corresponding authors)

A small molecule mitigates hearing loss in a mouse model of Usher syndrome III. Alagramam KN*, Gopal SR, Geng R, Chen DH, Nemet I, Lee R, Tian G, Miyagi M, Malagu KF, Lock CJ, Esmieu WR, Owens AP, Lindsay NA, Ouwehand K, Albertus F, Fischer DF, Bürli RW, MacLeod AM, Harte WE, Palczewski K, Imanishi Y*. Nat Chem Biol. 2016 Apr 25. doi: 10.1038/nchembio.2069. (* corresponding authors) (Featured by “News and Views” of the journal)

Impairment of vision in a mouse model of Usher Syndrome type III.  Tian G, Lee R, Ropelewski P, Imanishi Y. Invest Ophthalmol Vis Sci. 2016 Mar 1;57(3):866-75. doi: 10.1167/iovs.15-16946.

Organization of cGMP sensing structures on the rod photoreceptor outer segment plasma membrane.  Nemet I, Tian G, Imanishi Y. Channels (Austin). 2014;8(6):528-35. PubMed PMID: 25616687. (Invited research article, Featured by “News and Views” of the journal)

Retrograde intraciliary trafficking of opsin during the maintenance of cone-shaped photoreceptor outer segments of Xenopus laevis.  Tian G, Lodowski KH, Lee R, Imanishi Y. J Comp Neurol. 2014 Nov 1;522(16):3577-89. Featured on the cover

Submembrane Assembly and Renewal of Rod Photoreceptor cGMP-Gated Channel: Insight into the Actin-Dependent Process of Outer Segment Morphogenesis.  Nemet I, Tian G, Imanishi Y. J Neurosci. 2014 Jun 11;34(24):8164-74. Selected as a Featured Article in the Journal of Neuroscience

An unconventional secretory pathway mediates the cilia targeting of peripherin/rds.  Tian G, Ropelewski P, Nemet I, Lee R, Lodowski KH, and Imanishi Y. J. Neurosci. 2014 Jan 15;34 992-1006  Recommended by F1000Prime

Signals governing the trafficking and mis-trafficking of a ciliary GPCR, rhodopsin.  Lodowski KH, Lee R, Ropelewski P, Nemet I, Tian G, Imanishi Y. J Neurosci. 2013 Aug 21;33(34):13621-38.

The mechanosensory structure of the hair cell requires clarin-1, a protein encoded by Usher syndrome III causative gene.  Geng R, Melki S, Chen DH, Tian G, Furness DN, Oshima-Takago T, Neef J, Moser T, Askew C, Horwitz G, Holt JR, Imanishi Y, Alagramam KN. J Neurosci. 2012 Jul 11;32(28):9485-98.

Noninvasive multiphoton fluorescence microscopy resolves retinol and retinal condensation products in mouse eyes.  Palczewska G, Maeda T, Imanishi Y, Sun W, Chen Y, Williams DR, Piston DW, Maeda A, Palczewski K.  Nat Med. 2010 Dec;16(12):1444-9.

Clarin-1, encoded by the Usher syndrome III causative gene, forms a membranous microdomain: Possible role of Clarin-1 in organizing the actin cytoskeleton.  Tian G, Zhou Y, Hajkova D, Miyagi M, Dinculescu A, Hauswirth WW, Palczewski K, Geng R, Alagramam KN, Isosomppi J, Sankila EM, Flannery JG, Imanishi Y.  J Biol Chem. 2009 May 7.  doi:10.1074/jbc.M109.003160

Retinyl ester homeostasis in the adipose differentiation-related protein-deficient retina.  Imanishi Y*, Sun W, Maeda T, Maeda A, Palczewski K*.  J Biol Chem. 2008 Sep 5;283(36):25091-102. (* corresponding authors)

RBP4 disrupts vitamin A uptake homeostasis in a STRA6-deficient animal model for Matthew-Wood syndrome.  Isken A, Golczak M, Oberhauser V, Hunzelmann S, Driever W, Imanishi Y, Palczewski K, von Lintig J.  Cell Metab. 2008 Mar;7(3):258-68. Featured on the cover

Essential role of Ca²⁺-binding protein 4, a Ca_v1.4 channel regulator, for photoreceptor synaptic function.  Haeseleer F*, Imanishi Y*, Maeda T, Possin DE, Maeda A, Lee A, Rieke F, and Palczewski K.  Nature Neuroscience. 2004; Oct;7(10):1079-87. (*  authors contributed equally to the work) Recommended by F1000Prime

Diversity of guanylate cyclase-activating proteins (GCAPs) in teleost fish: Characterization of three novel GCAPs (GCAP4, GCAP5, GCAP7 ) from zebrafish (Danio Rerio) and prediction of eight GCAPs (GCAP1-8) in pufferfish (Fugu Rubripes).  Imanishi Y*, Yang L*, Sokal I, Filipek S, Palczewski K, Baehr W.  J Mol Evol. 2004; 59: 204-217 (*  authors contributed equally to the work)

Lecithin:retinol acyltransferase (LRAT) is essential for retention of retinyl esters in the eye and in the liver.  Batten ML*, Imanishi Y*, Maeda T*, Tu D, Moise AR, Bronson D, Possin D, Van Gelder RN, Baehr W, Palczewski K.  J Biol Chem. 2004 Mar 12;279(11):10422-32. (*  authors contributed equally to the work)

Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye.  Imanishi Y, Batten ML, Piston DW, Baehr W, Palczewski K.  J Cell Biol. 2004 Feb 2;164(3):373-83. Featured on the cover and by “In This Issue” of the journal

Dual-substrate specificity short chain retinol dehydrogenases from the vertebrate retina.  Haeseleer F*, Jang GF*, Imanishi Y*, Driessen CA, Matsumura M, Nelson P, Palczewski K.  J Biol Chem. 2002 Nov 22;277(47):45537-46. (*  authors contributed equally to the work)

Characterization of retinal guanylate cyclase-activating protein 3 (GCAP3) from zebrafish to man.  Imanishi Y, Li N, Sokal I, Sowa ME, Lichtarge O, Wensel TG, Saperstein DA, Baehr W, Palczewski K.  Eur. J. Neurosci. 2002;15(1):63-78. Featured on the cover