PUBLICATION
Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development
- Authors
- Seese, S.E., Muheisen, S., Gath, N., Gross, J.M., Semina, E.V.
- ID
- ZDB-PUB-221229-3
- Date
- 2022
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 252(4): 510-526 (Journal)
- Registered Authors
- Gath, Natalie, Gross, Jeffrey, Semina, Elena
- Keywords
- HSPA5, HSPA8, MAB21L2, co-factor, coloboma, zebrafish
- MeSH Terms
-
- Adult
- Animals
- Coloboma*/pathology
- Eye
- Eye Abnormalities*
- Eye Proteins/metabolism
- HSC70 Heat-Shock Proteins/genetics
- Humans
- Intracellular Signaling Peptides and Proteins
- Retina/metabolism
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- PubMed
- 36576422 Full text @ Dev. Dyn.
Citation
Seese, S.E., Muheisen, S., Gath, N., Gross, J.M., Semina, E.V. (2022) Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development. Developmental Dynamics : an official publication of the American Association of Anatomists. 252(4):510-526.
Abstract
Background Pathogenic variants in human MAB21L2 result in microphthalmia, anophthalmia and coloboma. The exact molecular function of MAB21L2 is currently unknown. We conducted a series of yeast two-hybrid (Y2H) experiments to determine protein interactomes of normal human and zebrafish MAB21L2/mab21l2 as well as human disease-associated variant MAB21L2-p.(Arg51Gly) using human adult retina and zebrafish embryo libraries.
Results These screens identified klhl31, tnpo1, TNPO2/tnpo2, KLC2/klc2, and SPTBN1/sptbn1 as co-factors of MAB21L2/mab21l2. Several factors, including hspa8 and hspa5, were found to interact with MAB21L2-p.Arg51Gly but not wild-type MAB21L2/mab21l2 in Y2H screens. Further analyses via 1-by-1 Y2H assays, co-immunoprecipitation and mass spectrometry revealed that both normal and variant MAB21L2 interact with HSPA5 and HSPA8. In situ hybridization detected co-expression of hspa5 and hspa8 with mab21l2 during eye development in zebrafish. Examination of zebrafish mutant hspa8hi138Tg identified reduced hspa8 expression associated with severe ocular developmental defects, including small eye, coloboma, and anterior segment dysgenesis. To investigate the effects of hspa8 deficiency on the mab21l2Arg51_Phe52del allele, corresponding zebrafish double mutants were generated and found to be more severely affected than single mutant lines.
Conclusion This study identifies heat shock proteins as interacting partners of MAB21L2/mab21l2 and suggest a role for this interaction in vertebrate eye development. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping