Faculty Collaboration Database

Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development. Dev Dyn 2023 Apr;252(4):510-526

Date

12/29/2022

Pubmed ID

36576422

Pubmed Central ID

PMC10947772

DOI

10.1002/dvdy.560

Scopus ID

2-s2.0-85145738490 (requires institutional sign-in at Scopus site)   2 Citations

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 hspa8^hi138Tg 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 mab21l2^{Arg51_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 suggests a role for this interaction in vertebrate eye development.

Author List

Seese SE, Muheisen S, Gath N, Gross JM, Semina EV

Author

Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Animals
Coloboma
Eye
Eye Abnormalities
Eye Proteins
HSC70 Heat-Shock Proteins
Humans
Intracellular Signaling Peptides and Proteins
Retina
Zebrafish
Zebrafish Proteins