# Role of secretory pathway kinases in visual long-term adaptation

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $243,000

## Abstract

Abstract
Neuronal systems must adapt to fast and slow changes in the environment. A classic example
is the visual system that can adjust to changes of several orders of magnitude in light levels
within just seconds. Adaptation on a much longer time scale has been observed as well upon
the shift from a regular light:dark cycle to continuous illumination. In Drosophila, this shift
triggers a reduced sensitivity to light and a down regulation of synaptic active zones in
photoreceptors. We recently discovered that the unfolded protein response (UPR) plays a major
role in regulating this adaptation. After just one night with continuous light exposure, both the
Ire1 and the PERK arm of the UPR exhibit strong activation. Interference with the normal
regulation of the UPR results in the loss of visual neurotransmission and severe structural
deterioration of rhabdomeres, the microvillar arrays that house the key elements of the
phototransduction cascade. This phenotype was observed for fic and BiP mutants that interfere
with the regulation of the activity of BiP, a major regulator of the UPR. Screening for additional
elements of this pathway, we identified an unconventional kinase, called Allnighter (Aln), as a
candidate. Its sequence predicts this kinase to be acting in the secretory pathway. Preliminary
data indicate that, similar to fic and BiP mutants, continued illumination causes aln mutants to
lose visual neurotransmission and structural integrity of rhabdomeres. This proposal aims to
characterize the role of aln in long-term visual adaption (i) by defining its subcellular and cell-
type specific side of action, (ii) by testing its role in regulating the Ire1 or PERK arms of the
UPR, and (iii) by identifying Aln substrates necessary for long-term visual adaption. Completion
of these experiments will significantly enhance our understanding of the mechanism by which
the UPR aids in the maintenance of visual acuity during long-term adaption.

## Key facts

- **NIH application ID:** 10003286
- **Project number:** 5R21EY030785-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Helmut J Kramer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,000
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003286

## Citation

> US National Institutes of Health, RePORTER application 10003286, Role of secretory pathway kinases in visual long-term adaptation (5R21EY030785-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10003286. Licensed CC0.

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