DAB1

Official Full Name

DAB adaptor protein 1

Organism

Homo sapiens

GeneID

1600

Background

The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. [provided by RefSeq, Jan 2017]

Synonyms

SCA37;

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Detailed Information

Dab, reelin signal transducer, homolog 1 (Drosophila) (Dab1) is a multifunctional protein involved in essential cellular processes, including cell adhesion, migration, and neuronal development. Dab1, a key player in reelin signaling, is a conserved adapter protein critical for brain development and neuronal migration.

Structure And Domain Organization of Dab1

The DAB1 gene is a key regulator of multiple cellular processes, playing a significant role in the immune system and synaptic function. Its structure consists of 10 exons and 9 introns, encoding a protein of 363 amino acids. The gene is highly conserved across different species, highlighting its essential function in organismal survival. Aberrations in the DAB1 gene have been associated with various neurological and autoimmune disorders.

Functions of Dab1

Dab1 acts as a central hub in reelin signaling, influencing neuronal positioning, synaptogenesis, and dendritic branching. Moreover, it plays a role in non-neuronal tissues, participating in cell adhesion and migration processes. The DAB1 gene is a crucial regulator of multiple cellular processes, playing a significant role in the immune system and synaptic function. It encodes a protein that serves as a receptor for the cytokine RhoA, which is involved in various cellular activities such as cell migration, differentiation, and apoptosis. DAB1 is also essential for the proper development and function of the central nervous system.

Dab Participation in Phosphorylation Plays a Role in Neurons

The Dab1 gene plays a crucial role in phosphorylation processes within the cell. This gene encodes a protein that functions as a signal transduction molecule, participating in various cellular pathways including neuronal development and synaptic plasticity. The protein exhibits receptor-like properties, binding to ligands such as reelin, which is essential for proper neuronal positioning and function.The Dab protein undergoes phosphorylation, a post-translational modification that alters its activity and substrate specificity. Phosphorylation occurs at multiple sites within the protein, resulting in distinct conformational changes that regulate its interaction with other cellular components. These phosphorylation events are precisely controlled during development and adulthood, ensuring proper neuronal function and survival.Additionally, In the developing nervous system, Dab phosphorylation plays a critical role in neuronal migration and axon guidance. For instance, it interacts with the lipid phosphatidylinositol 3-kinase (PI3K) signaling pathway, which regulates cell migration, synaptic plasticity, and neurogenesis. Phosphorylation of Dab at specific sites activates PI3K, triggering a cascade of downstream signaling events that control neuronal development and function.

Dab Gene Causes Multiple Neurological Disorders

The Dab1 gene has been implicated in various neurological disorders due to its crucial role in neuronal development, migration, and synaptic plasticity. Disorders such as autism spectrum disorder (ASD), intellectual disability, and cerebrovascular diseases have been associated with abnormal Dab function and regulation. Mutations in the Dab gene can lead to impairments in neuronal migration and connectivity, resulting in abnormal brain structure and function. These mutations can cause changes in the phosphorylation status of the Dab protein, leading to dysregulated signaling pathways that are crucial for neural development. In addition, dysregulated Dab phosphorylation has been linked to altered synaptic plasticity, a key mechanism underlying learning and memory. Impaired synaptic plasticity is a common feature in neurological disorders such as Alzheimer's disease and schizophrenia.

References:

Assadi AH, Zhang G, Beffert U, McNeil RS, Renfro AL, Niu S, Quattrocchi CC, Antalffy BA, Sheldon M, Armstrong DD, Wynshaw-Boris A, Herz J, D'Arcangelo G, Clark GD (2003) Interaction of reelin signaling and Lis1 in brain development. Nat Genet 35:270–276. - PubMed
Ballif BA, Arnaud L, Arthur WT, Guris D, Imamoto A, Cooper JA (2004) Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. Curr Biol 14:606–610. - PubMed
Bar I, Lambert De Rouvroit C, Royaux I, Krizman DB, Dernoncourt C, Ruelle D, Beckers MC, Goffinet AM (1995) A YAC contig containing the reeler locus with preliminary characterization of candidate gene fragments. Genomics 26:543–549. - PubMed

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