An alternative N-terminal fold of the intestine-specific annexin A13a induces dimerization and regulates membrane-binding

McCulloch, K.M.; Yamakawa, Izumi; Shifrin, David A.; McConnell, Russell E.; Foegeding, Nora J.; Singh, Prashant K.; Mao, Suli; Tyska, Matthew J.; Iverson, T.M.

doi:10.1074/jbc.ra118.004571

Cited by 11 publications

(7 citation statements)

References 45 publications

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“…The underlying mechanism of their transportation and function at the tips of stereocilia remain elusive. In the intestine, annexin A13 (ANXA13) is localized at the tips of microvilli, the actin-based cell protrusions similar to stereocilia ( McCulloch et al, 2019 ). The function of ANXA13 at the tips of microvilli is still unknown, but this localization is consistent with a possible role in lumenal vesicle formation ( McConnell et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Annexin A4 Is Dispensable for Hair Cell Development and Function

et al. 2021

Front. Cell Dev. Biol.

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Annexin A4 (ANXA4) is a Ca2+-dependent phospholipid-binding protein that is specifically expressed in the cochlear and vestibular hair cells, but its function in the hair cells remains unknown. In the present study, we show that besides localizing on the plasma membrane, ANXA4 immunoreactivity is also localized at the tips of stereocilia in the hair cells. In order to investigate the role of ANXA4 in the hair cells, we established Anxa4 knockout mice using CRISPR/Cas9 technique. Unexpectedly, the development of both cochlear and vestibular hair cells is normal in Anxa4 knockout mice. Moreover, stereocilia morphology of Anxa4 knockout mice is normal, so is the mechano-electrical transduction (MET) function. Consistently, the auditory and vestibular functions are normal in the knockout mice. In conclusion, we show here that ANXA4 is dispensable for the development and function of hair cells, which might result from functional redundancy between ANXA4 and other annexin(s) in the hair cells.

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Section: Discussionmentioning

confidence: 99%

Annexin A4 Is Dispensable for Hair Cell Development and Function

et al. 2021

Front. Cell Dev. Biol.

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“…Proteins in this family contain two major domains, one at the C-terminus for the Ca 2+ binding effect, and the other at the N-terminus responsible for the membrane interactions. While the core domain at the C-terminus is highly conserved across the gene family, the N-terminus is variable 47 , allowing for tissue-specific regulation 48, 49 and localization 50 .The two known forms of the gene differ only in the length of the last helical structure, where the incorporation of additional peptides allows for an extension of the first helix.…”

Section: Finding Novel Orfs In Assembled Rna-seq Datamentioning

confidence: 99%

Investigating Open Reading Frames in Known and Novel Transcripts using ORFanage

Varabyou

Erdogdu

Salzberg

et al. 2023

Preprint

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ORFanage is a system designed to assign open reading frames (ORFs) to both known and novel gene transcripts while maximizing similarity to annotated proteins. The primary intended use of ORFanage is the identification of ORFs in the assembled results of RNA sequencing (RNA-seq) experiments, a capability that most transcriptome assembly methods do not have. Our experiments demonstrate how ORFanage can be used to find novel protein variants in RNA-seq datasets, and to improve the annotations of ORFs in tens of thousands of transcript models in the RefSeq and GENCODE human annotation databases. Through its implementation of a highly accurate and efficient pseudo-alignment algorithm, ORFanage is substantially faster than other ORF annotation methods, enabling its application to very large datasets. When used to analyze transcriptome assemblies, ORFanage can aid in the separation of signal from transcriptional noise and the identification of likely functional transcript variants, ultimately advancing our understanding of biology and medicine.

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“…Its expression is tightly restricted to intestine, and transcribed as two isoforms by alternative splicing (named A13a and A13b) ( Iglesias et al, 2001 ; Gerke and Moss, 2002 ). Of note, it is the only member myristoylated at its N-terminal domain, allowing specific membrane association features that may act synergistically with canonical ( Gerke and Moss, 2002 ; Turnay et al, 2005 ; McCulloch et al, 2019 ). Like other annexins, ANXA13 is involved in membrane biology, being of special relevance in lipid-raft dynamics involved in apical transport ( Lafont et al, 1998 ; Plant et al, 2000 ).…”

Section: Annexin A13mentioning

confidence: 99%

Pathobiological functions and clinical implications of annexin dysregulation in human cancers

Prieto-Fernández

Menéndez

Otero-Rosales

et al. 2022

Front. Cell Dev. Biol.

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Annexins are an extensive superfamily of structurally related calcium- and phospholipid-binding proteins, largely conserved and widely distributed among species. Twelve human annexins have been identified, referred to as Annexin A1-13 (A12 remains as of yet unassigned), whose genes are spread throughout the genome on eight different chromosomes. According to their distinct tissue distribution and subcellular localization, annexins have been functionally implicated in a variety of biological processes relevant to both physiological and pathological conditions. Dysregulation of annexin expression patterns and functions has been revealed as a common feature in multiple cancers, thereby emerging as potential biomarkers and molecular targets for clinical application. Nevertheless, translation of this knowledge to the clinic requires in-depth functional and mechanistic characterization of dysregulated annexins for each individual cancer type, since each protein exhibits varying expression levels and phenotypic specificity depending on the tumor types. This review specifically and thoroughly examines the current knowledge on annexin dysfunctions in carcinogenesis. Hence, available data on expression levels, mechanism of action and pathophysiological effects of Annexin A1-13 among different cancers will be dissected, also further discussing future perspectives for potential applications as biomarkers for early diagnosis, prognosis and molecular-targeted therapies. Special attention is devoted to head and neck cancers (HNC), a complex and heterogeneous group of aggressive malignancies, often lately diagnosed, with high mortality, and scarce therapeutic options.

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An alternative N-terminal fold of the intestine-specific annexin A13a induces dimerization and regulates membrane-binding

Cited by 11 publications

References 45 publications

Annexin A4 Is Dispensable for Hair Cell Development and Function

Annexin A4 Is Dispensable for Hair Cell Development and Function

Investigating Open Reading Frames in Known and Novel Transcripts using ORFanage

Pathobiological functions and clinical implications of annexin dysregulation in human cancers

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