Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Int J Dermatol ; 58(8): 946-952, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31077348

ABSTRACT

BACKGROUND: Autosomal recessive wooly hair/hypotrichosis is an inherited disorder of hair characterized by less dense, short, and tightly curled hair on the scalp and sometimes less dense to complete absence of eyebrows and eyelashes. Autosomal recessive wooly hair/hypotrichosis phenotypes are mostly associated with pathogenic sequence variants in LIPH and LPAR6 genes. METHODS: To find out the molecular basis of the disease, five families with autosomal recessive wooly hair/hypotrichosis were recruited for genetic analysis. Direct Sanger sequencing of LIPH and LPAR6 genes was carried out using BigDye chain termination chemistry. P2RY5 protein homology models were developed to study the effect of mutation on protein structure in a family having novel mutation. RESULTS: Sanger sequencing revealed a novel homozygous missense mutation (c.47A>T) in the LPAR6 gene in family A, while recurrent mutation (c.436G>A) was detected in the rest of the four families (B-E). Protein homology models for both native and mutant P2RY5 protein were developed to study the difference in subtle structural features because of Lys16Met (K16M) mutation. We observed that P2RY5K16M mutation results decrease in the number of ionic interactions detrimental to the protein stability. Protein modeling studies revealed that the novel mutation identified here decreased the number of ionic interactions by affecting physicochemical parameters of the protein, leading to an overall decrease in protein stability with no major secondary structural changes. CONCLUSION: The molecular analysis further confirms the frequent involvement of LPAR6 in autosomal recessive wooly hair/hypotrichosis, while the bioinformatic study revealed that the missense mutation destabilizes the overall structure of P2RY5 protein.


Subject(s)
Genes, Recessive/genetics , Hair Diseases/genetics , Hair/abnormalities , Hypotrichosis/genetics , Receptors, Lysophosphatidic Acid/genetics , Computational Biology , Consanguinity , Female , Humans , Male , Mutation, Missense , Pakistan , Pedigree , Phenotype , Protein Structure, Secondary/genetics , Receptors, Lysophosphatidic Acid/chemistry , Receptors, Purinergic P2/chemistry , Receptors, Purinergic P2/genetics , Sequence Homology, Amino Acid
2.
Microbiol Spectr ; 4(4)2016 08.
Article in English | MEDLINE | ID: mdl-27726772

ABSTRACT

During an innate immune response, myeloid cells undergo complex morphological adaptations in response to inflammatory cues, which allow them to exit the vasculature, enter the tissues, and destroy invading pathogens. The actin and microtubule cytoskeletons are central to many of the most essential cellular functions including cell division, cell morphology, migration, intracellular trafficking, and signaling. Cytoskeletal structure and regulation are crucial for many myeloid cell functions, which require rapid and dynamic responses to extracellular signals. In this chapter, we review the roles of the actin and microtubule cytoskeletons in myeloid cells, focusing primarily on their roles in chemotaxis and phagocytosis. The role of myeloid cell cytoskeletal defects in hematological disorders is highlighted throughout.


Subject(s)
Cytoskeleton/metabolism , Immunity, Innate , Myeloid Cells/physiology , Animals , Chemotaxis , Humans , Phagocytosis
SELECTION OF CITATIONS
SEARCH DETAIL
...