KATNAL2

Official Full Name

katanin catalytic subunit A1 like 2

Organism

Homo sapiens

GeneID

83473

Background

Predicted to enable ATP hydrolysis activity. Predicted to be involved in cytoplasmic microtubule organization. Located in cytoplasm; microtubule; and spindle pole. [provided by Alliance of Genome Resources, Feb 2025]

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Detailed Information

Recent Research

Microtubules (MTs) are dynamic cytoskeletalpolymers critical for the form and function of numerous subcellular structures, including spindles and cilia. One major class of MT-severing enzyme is Katanins. Katanin-like protein 2 (KATNAL2) has functional relevance for multiple MT-dependent cellular processes: knockdown of KATNAL2 results in defective ciliogenesis, ineﬃcient cytokinesis, enlarged cellular and nuclear size, increased number of centrioles, formation of aberrant multipolar mitotic spindles, mitotic defects, chromosome bridges, multinucleated cells, increased MT acetylation, and an altered cell cycle. KATNAL2 was expressed in a wide array of ciliated and neural tissues throughout development. It was localized to ciliary axonemes, basal bodies, centrioles, and spindles, and was required for ciliogenesis and correct brain development.

KATNAL2 consists of five alternatively spliced isoforms encoded by the KATNAL2 genomic locus. In vivo these isoforms are able to interact with themselves, with each other and moreover directly and independently with MRP/MinD-type P-loop NTPases Nubp1 and Nubp2, which are integral components of centrioles, negative regulators of ciliogenesis and implicated in centriole duplication in mammalian cells. The ciliogenesis-promoting activity of KATNAL2 may be inhibited by interactions with the NUBP proteins under cycling conditions. Silencing or stable over-expression of KATNAL2 isoforms drastically reduces ciliogenesis.

KATNAL2 is critical for numerous aspects of spermiogenesis, including the initiation of the axoneme from the basal body, suppression of the spermatid centriole duplication cycle, sperm nuclear sculpting via the manchette, the attachment of the acrosome to the nucleus and the tethering of elongated spermatids to Sertoli cells (SC) via the tubulobulbar complex and ultimately sperm release via spermiation.It is achieved by KATNAL2 acting in partnership with KATNB1, a known regulator of other katanin severing proteins, or via KATNB1-independent mechanisms.KATNAL2 can bind to the non-classical tubulin subunits δ-and ε-tubulin, such interactions occur in both the manchette and the basal body region of haploid male germ cells.Loss of functional KATNAL2 results in several phenotypes which are outwardly consistent with a loss of microtubule regulation e.g. abnormal elongation and delayed disassembly of the manchette microtubules and a failure of the manchette to move distally during elongated spermatid development. KATNAL2’s actions at the basal body, is achieved in a KATNB1-independent manner. KATNAL2-KATNB1 complexes were not localized to the basal body, despite clear regulation of the basal body by KATNAL2 in spermatids. This regulation is consistent with recent data suggesting that KATNAL2 interacts with the well-characterized centriole proteins CEP97, CEP295 and CDK5RAP2.Furthermore, KATNAL2 has been identiﬁed as a risk gene for autism spectrum disorders (ASD).

References:

Jem D, et al. Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse. Plos Genetics, 2017, 13(11):e1007078.
Ververis A, et al. A novel family of katanin-like 2 protein isoforms (KATNAL2), interacting with nucleotide-binding proteins Nubp1 and Nubp2, are key regulators of different MT-based processes in mammalian cells. Cellular & Molecular Life Sciences, 2016, 73(1):163-184.
Helen R W, et al, Katanin-like protein Katnal2 is required for ciliogenesis and braindevelopment in Xenopus embryos.Developmental Biology, 2018, 8:2-10.

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