Localization and genetic analysis of mind-meld gene in Drosophila melanogaster
Advisor Information
Bruce Chase
Location
UNO Criss Library, Room 112
Presentation Type
Oral Presentation
Start Date
7-3-2014 2:00 PM
End Date
7-3-2014 2:15 PM
Abstract
The ADAM (a disintegrin and metalloprotease domain) proteins comprise a family of membrane-anchored proteins able to disrupt integrin-mediated cell-cell interactions. About half of all known ADAM proteins have active metalloprotease domains that can process and shed ectodomains of membrane-anchored growth factors, cytokines and receptors. In this way, they serve a major role during development (e.g., kuz encodes an ADAM protein that serves such a role in Notch signaling). The role of ADAMs without metalloprotease function is less well understood. The Drosophila mind-meld (mmd) gene encodes transcripts that are highly expressed in the developing and adult central nervous system and encode proteins with extensive sequence similarity to human ADAM22, ADAM23, and ADAM11. Its transcripts undergo extensive alternative mRNA splicing to produce at least four different protein isoforms: one secreted and three membrane-bound proteins differing in their intracellular cytoplasmic domains. All are likely to lack a functional metalloprotease, as they have a single amino-acid change from a required consensus. To better understand these isoforms’ role in the developing and formed nervous system, their expression is was evaluated using immunostaining with antibodies generated against isoform-specific epitopes and RNAi is being used to discover whether they specific isoforms are required for normal nervous system structure or behavior. Knockdown in the retina is associated with defects in the adult pseudopupil. The detailed nature of the underlying morphological defects, and whether they are developmental or reflect neurodegeneration following normal development is under investigation.
Localization and genetic analysis of mind-meld gene in Drosophila melanogaster
UNO Criss Library, Room 112
The ADAM (a disintegrin and metalloprotease domain) proteins comprise a family of membrane-anchored proteins able to disrupt integrin-mediated cell-cell interactions. About half of all known ADAM proteins have active metalloprotease domains that can process and shed ectodomains of membrane-anchored growth factors, cytokines and receptors. In this way, they serve a major role during development (e.g., kuz encodes an ADAM protein that serves such a role in Notch signaling). The role of ADAMs without metalloprotease function is less well understood. The Drosophila mind-meld (mmd) gene encodes transcripts that are highly expressed in the developing and adult central nervous system and encode proteins with extensive sequence similarity to human ADAM22, ADAM23, and ADAM11. Its transcripts undergo extensive alternative mRNA splicing to produce at least four different protein isoforms: one secreted and three membrane-bound proteins differing in their intracellular cytoplasmic domains. All are likely to lack a functional metalloprotease, as they have a single amino-acid change from a required consensus. To better understand these isoforms’ role in the developing and formed nervous system, their expression is was evaluated using immunostaining with antibodies generated against isoform-specific epitopes and RNAi is being used to discover whether they specific isoforms are required for normal nervous system structure or behavior. Knockdown in the retina is associated with defects in the adult pseudopupil. The detailed nature of the underlying morphological defects, and whether they are developmental or reflect neurodegeneration following normal development is under investigation.