PMID- 24046442
OWN - NLM
STAT- MEDLINE
DCOM- 20140731
LR  - 20181202
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 126
IP  - Pt 23
DP  - 2013 Dec 1
TI  - Activity-dependent secretion of progranulin from synapses.
PG  - 5412-21
LID - 10.1242/jcs.132076 [doi]
AB  - The secreted growth factor progranulin (PGRN) has been shown to be important for 
      regulating neuronal survival and outgrowth, as well as synapse formation and 
      function. Mutations in the PGRN gene that result in PGRN haploinsufficiency have 
      been identified as a major cause of frontotemporal dementia (FTD). Here we 
      demonstrate that PGRN is colocalized with dense-core vesicle markers and is 
      co-transported with brain-derived neurotrophic factor (BDNF) within axons and 
      dendrites of cultured hippocampal neurons in both anterograde and retrograde 
      directions. We also show that PGRN is secreted in an activity-dependent manner 
      from synaptic and extrasynaptic sites, and that the temporal profiles of 
      secretion are distinct in axons and dendrites. Neuronal activity is also shown to 
      increase the recruitment of PGRN to synapses and to enhance the density of PGRN 
      clusters along axons. Finally, treatment of neurons with recombinant PGRN is 
      shown to increase synapse density, while decreasing the size of the presynaptic 
      compartment and specifically the number of synaptic vesicles per synapse. 
      Together, this indicates that activity-dependent secretion of PGRN can regulate 
      synapse number and structure.
FAU - Petoukhov, Eugenia
AU  - Petoukhov E
AD  - Department of Cellular and Physiological Sciences and the Brain Research Centre, 
      University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T-1Z3, 
      Canada.
FAU - Fernando, Sarah
AU  - Fernando S
FAU - Mills, Fergil
AU  - Mills F
FAU - Shivji, Farhan
AU  - Shivji F
FAU - Hunter, Diana
AU  - Hunter D
FAU - Krieger, Charles
AU  - Krieger C
FAU - Silverman, Michael A
AU  - Silverman MA
FAU - Bamji, Shernaz X
AU  - Bamji SX
LA  - eng
GR  - MOP-81158/Canadian Institutes of Health Research/Canada
GR  - MOP-90396/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130917
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Grn protein, rat)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Progranulins)
RN  - 0 (Protein Precursors)
SB  - IM
MH  - Animals
MH  - Axons/*metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Dendrites/*metabolism
MH  - Embryo, Mammalian
MH  - Gene Expression
MH  - Hippocampus/cytology/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Progranulins
MH  - Protein Precursors/genetics/*metabolism
MH  - Protein Transport
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Secretory Vesicles/metabolism
MH  - Synapses/metabolism
MH  - Synaptic Vesicles/metabolism
OTO - NOTNLM
OT  - Activity
OT  - Frontotemporal dementia
OT  - Hippocampal culture
OT  - Progranulin
OT  - Protein trafficking
OT  - Secretion
OT  - Synapses
EDAT- 2013/09/21 06:00
MHDA- 2014/08/01 06:00
CRDT- 2013/09/19 06:00
PHST- 2013/09/19 06:00 [entrez]
PHST- 2013/09/21 06:00 [pubmed]
PHST- 2014/08/01 06:00 [medline]
AID - jcs.132076 [pii]
AID - 10.1242/jcs.132076 [doi]
PST - ppublish
SO  - J Cell Sci. 2013 Dec 1;126(Pt 23):5412-21. doi: 10.1242/jcs.132076. Epub 2013 Sep 
      17.