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Pathway for trafficking of surfactant protein A (SP‐A) to lamellar bodies
Author(s) -
Dodia Chandra,
Kazi Altaf,
Bates Sandra R,
Fisher Aron B
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a553
Subject(s) - pulmonary surfactant , lamellar granule , chemistry , secretion , surfactant protein d , clathrin , endocytosis , biochemistry , microbiology and biotechnology , biology , receptor , innate immune system
SP‐A in the alveolar space is endocytosed by type II cells through a clathrin dependent pathway and is targeted to lamellar bodies (LB) for resecretion. Our previous studies (Jain et.al, AJP : 289 :, 2005) showed that amantidine, a clathrin inhibitor, can effectively block the contribution of endocytosed material to LB SP‐A content. To study trafficking of newly synthesized SP‐A, isolated rat lungs were perfused for 6 hrs with 35 S‐methionine ± amantadine and then surfactant and LB fractions were isolated from lavage and lung homogenate, respectively. SP‐A in isolated surfactant was 54% and in LB 19% of total protein and was similar in the presence or absence of amantidine. In control lungs, the sp. act. (dpm/mg SP‐A) was 6400±147 in LB and 4256±93 in surfactant under basal conditions and 10,408101 in LB and 6426±169 in surfactant in the presence of 0.1mM 8‐Br‐cAMP. Amantidine had no effect on SP‐A sp. act. in either fraction under either basal or stimulated conditions. These studies indicate that the sp. act. of 35 S‐ SP‐A at 6 h perfusion is higher in LB than surfactant suggesting a precursor‐product relationship. The failure of amantidine to alter the appearance of 35 S‐SPA in LB indicates that newly synthesized SP‐A is transferred from the ER directly to the secretory organelle prior to secretion. [HL19737].