June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
ER-resident BH3-only protein, BNip1, induces apoptosis in response to excessive activation of vesicular transport in zebrafish photoreceptors
Author Affiliations & Notes
  • Yuko Nishiwaki
    Developmental Neurobiology Unit, Okinawa Institute of Science and Technology, Kunigami-gun, Okinawa, Japan
  • Miyuki Suenaga
    Developmental Neurobiology Unit, Okinawa Institute of Science and Technology, Kunigami-gun, Okinawa, Japan
  • Masato Araragi
    Developmental Neurobiology Unit, Okinawa Institute of Science and Technology, Kunigami-gun, Okinawa, Japan
  • Ichiro Masai
    Developmental Neurobiology Unit, Okinawa Institute of Science and Technology, Kunigami-gun, Okinawa, Japan
  • Footnotes
    Commercial Relationships   Yuko Nishiwaki, None; Miyuki Suenaga, None; Masato Araragi, None; Ichiro Masai, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4538. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Yuko Nishiwaki, Miyuki Suenaga, Masato Araragi, Ichiro Masai; ER-resident BH3-only protein, BNip1, induces apoptosis in response to excessive activation of vesicular transport in zebrafish photoreceptors. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4538.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : In zebrafish, a BH3-only SNARE protein, BNip1, induces photoreceptor (PR) apoptosis in response to vesicular fusion defects (Nishiwaki et al. (2013) Dev Cell 25, 374-387). The aim of our research is to elucidate physiological roles of BNip1 in PR apoptosis.

Methods : In zebrafish photoreceptors, β-SNAP regulates vesicular fusion process. In zebfrafish β-SNAP mutant, photoreceptors undergo BNip1-dependent apoptosis. Here, we examined a critical period of BNip1-dependent PR apoptosis in zebrafish. In β-SNAP mutant, PR degeneration mainly occurs in 2–3 days post-fertilization (dpf) when protein transport to the outer segment is highly activated. β-SNAP was overexpressed under the control of heat-shock promoter in different time windows and examined which time window PR apoptosis was rescued. Next, we decreased the level of protein transport through the connecting cilium to the outer segment in the β-SNAP mutant by injection of morpholino- antisense oligos for intra-flagella transport regulator, IFT88 and Kif3b, and examined whether PR apoptosis was inhibited at 3.5 dpf.

Results : Overexpression of β-SNAP after 48 hpf rescued PR apoptosis, whereas overexpression after 72 hpf did not recover PR survival. These data suggest that 48–72 hpf is the critical period for BNip1-dependent PR apoptosis. Next, we over-expressed β-SNAP only in the embryonic stage from 1 to 5 dpf, bred larvae by 21 dpf, and examined PR apoptosis. In this case, PRs survived. Thus, β-SNAP activity in 2–5 dpf is enough to maintain PRs until 21 dpf. Furthermore, the blockade of IFT88- and Kif3b-depedent protein transport also rescued PR apoptosis in zebrafish β-SNAP mutants.

Conclusions : Our data indicate that the depletion of β-SNAP activates BNip1-dependent apoptosis in zebrafish PRs during PR differentiation, in which photoreceptive proteins are actively synthesized and transported to the outer segment. Furthermore, when protein transport to the outer segment is inhibited, PR survival is recovered in the β-SNAP mutant. We propose that BNip1 functions as a safe guard mechanism that inhibits excessive activation of vesicular transport during PR differentiation.

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

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×