CAPS1 regulates catecholamine loading of large dense-core vesicles.
CAPS1 is thought to play an essential role in mediating exocytosis from large dense-core vesicles (LDCVs). We generated CAPS1-deficient (KO) mice and studied exocytosis in a model system for Ca2+-dependent LDCV secretion, the adrenal chromaffin cell. Adult heterozygous CAPS1 KO cells display a gene dosage-dependent decrease of CAPS1 expression and a concomitant reduction in the number of docked vesicles and secretion. Embryonic homozygous CAPS1 KO cells show a strong reduction in the frequency of amperometrically detectable release events of transmitter-filled vesicles, while the total number of fusing vesicles, as judged by capacitance recordings or total internal reflection microscopy, remains unchanged. We conclude that CAPS1 is required for an essential step in the uptake or storage of catecholamines in LDCVs.
Speidel
Dina
D
Max-Planck-Institut für Experimentelle Medizin, Abteilung Molekulare Neurobiologie, D-37075 Göttingen, Germany.
Bruederle
Cathrin E
CE
Enk
Carsten
C
Voets
Thomas
T
Varoqueaux
Frederique
F
Reim
Kerstin
K
Becherer
Ute
U
Fornai
Francesco
F
Ruggieri
Stefano
S
Holighaus
Yvonne
Y
Weihe
Eberhard
E
Bruns
Dieter
D
Brose
Nils
N
Rettig
Jens
J
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005089:Exocytosis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D022142:Secretory Vesicles / Q000502:physiology*
D002135:Calcium-Binding Proteins; D002395:Catecholamines; D009419:Nerve Tissue Proteins